Abstract
The progressive destruction of articular cartilage is one of the hallmarks of osteoarthritis and rheumatoid arthritis. Cartilage degradation is attributed to different classes of catabolic factors, including proinflammatory cytokines, aggrecanases, matrix metalloproteinases, and nitric oxide. Recently, matrix degradation products generated by excessive proteolysis in arthritis have been found to mediate cartilage destruction. These proteolytic fragments activate chondrocytes and synovial fibroblasts via specific cell surface receptors that can stimulate catabolic intracellular signaling pathways, leading to the induction of such catalysts. This review describes the catabolic activities of matrix degradation products, especially fibronectin fragments, and discusses the pathologic implication in cartilage destruction in osteoarthritis and rheumatoid arthritis. Increased levels of these degradation products, found in diseased joints, may stimulate cartilage breakdown by mechanisms of the kind demonstrated in the review.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
The extracellular matrix of cartilage is primarily composed of the large proteoglycan aggrecan and fibrils containing type-II collagen.1 Type-II collagen, composed of a triple helix of three identical α chains, forms fibrils stabilized by intermolecular crosslinks.2 The fibrils provide tensile strength and serve to constrain the swelling of aggrecan that endows cartilage with its compressive stiffness.1,3,4 Progressive destruction of cartilage, which results from an imbalance between the anabolic and catabolic processes, is a common feature of rheumatoid arthritis (RA) and osteoarthritis (OA). Proteoglycan loss that is observed in the development of early OA5,6 results in a reduction in cartilage stiffness.7,8 Degradation and loss of type-II collagen, which are observed in RA and OA,9,10 result in an irreversible loss of tensile properties and structural integrity.8 It is well known that proinflammatory cytokines including interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) have been shown to promote cartilage degradation by stimulating the production of matrix metalloproteinases (MMPs).11
The importance of understanding cell-matrix interactions at the level of regulation of matrix turnover is becoming very apparent. In addition to the proinflammatory cytokines, there is an increasing body of evidence that degradation products of cartilage matrix are another amplifier or catalyst in diseased joints, including RA and OA. This review focuses on the mechanism of cartilage destruction induced by matrix degradation products, especially by fibronectin fragments (FN-fs).
Structure of fibronectin
Fibronectin (FN) is an adhesive dimeric glycoprotein of 450kDa found in the extracellular matrix of many tissues, including normal cartilage12 and synovial membrane.13 It is also present in such body fluids as synovial fluid and plasma. As shown in Fig. 1, FN consists predominantly of three types of homologous repeating segments (designated I, II, and III). Significant protein heterogeneity results from the alternative splicing of a single RNA.14,15 The glycoprotein regulates functions of cellular adhesion and spreading, cell motility, cell growth, and differentiation and opsonization.16 FN contains amino (NH2)-terminal heparin-, gelatin-, celland carboxyl (COOH)-terminal heparin-binding domains. The central cell-binding region has an Arg-Gly-Asp (RGD) sequence in domain III10, recognized by several cell surface integrin family members.17 Several sites in the heparin-binding domain that are COOH-terminal to the central cell-binding domain also interact with the cell surface. Several peptides from domain III12–14 support cell attachment with varying affinities.18–23 The IIICS, or the variable (V) region, contains the integrin-binding sites, CS-1 and CS-5.24–28
Fibronectin fragments in OA and RA
Elevated levels of FN are found in OA cartilage29–31 and in OA synovial fluid.31,32 While FN is ubiquitous within active rheumatoid synovium, enhanced accumulation of FN is found on the inflamed synovial and pannus surfaces in the knee joints of patients with RA.33,34 Fibronectin is readily degraded into fragments by proteinases. Thus, activation of extracellular proteolysis in OA and RA may lead to the fragmentation of FN, indicating that FN-fs could be generated in vivo within cartilage and synovial fluid. Indeed, increased levels of FN-fs of 30–200 kDa are found in cartilage and synovial fluid from patients with OA and RA.31,32 In OA synovial fluids, FN-fs of 100–200kDa are found at approximately 1µM.32 The levels of FN-fs in OA cartilage are suggested to be similar to those in OA synovial fluids.31 The FN-f concentrations that have been used in in vitro studies are less than 1µM, similar to the levels in in vivo diseased joints. Since FN-fs can penetrate into cartilage tissue in vitro,35 FN-fs in OA and RA cartilages may include the fragments from synovial fluid.
Cartilage destruction by fibronectin fragments
Native FN has various biologic functions including cell attachment, cell migration, wound healing, and oncogenic transformation.14 However, native FN has no catabolic effect on cartilage.36,37 Once FN is fragmented, those proteolytic fragments acquire catalytic activities. Of FN-fs, the central cell-, NH2-terminal heparin-, and NH2-terminal gelatin-binding fragments of FN have been shown to stimulate cartilage chondrolysis.36 Recently, COOH-terminal heparin-binding FN-f has also been found to induce cartilage destruction.37 Removal of FN and FN-fs from OA synovial fluid can diminish cartilage-damaging activity,31 whereas injection of FN-fs into rabbit knee joints induces depletion of cartilage proteoglycan.38 These findings support the pathophysiological significance of FN-fs.
Proteoglycan degradation by fibronectin fragments
Increased aggrecan degradation1 is commonly observed in OA and RA. Homandberg et al. demonstrated for the first time that NH2-terminal heparin-, NH2-terminal gelatin-, and central cell-binding FN-fs enhance proteoglycan loss from bovine cartilage36 and decrease proteoglycan synthesis.39 In addition, COOH-terminal heparin-binding FN-f can promote loss of proteoglycan in bovine cartilage.37
Degradation of aggrecan that occurs early in cartilage damage is caused by aggrecanases40,41 and MMPs.42 Neoepitope antibodies specific for aggrecanase- or MMP-degraded aggrecan fragments distinguish between these activities in vivo.42 Anti-ITEGE373 and anti-A374RGSV antibodies identify aggrecanase cleavage site in the aggrecan interglobular domain, whereas anti-DIPEN341 and anti-F342FGVG antibodies detect MMP cleavage site in the same region. Both sites of aggrecanase cleavage are found in OA and RA cartilage.43 Treatment with NH2-terminal gelatinbinding FN-f results in the generation of aggrecanasederived ITEGE373 neoepitope in porcine cartilage.44 Amino acid sequencing of aggrecan from cartilage with treatment with NH2-terminal heparin-binding FN-f also confirms cleavage at the aggrecanase site in bovine cartilage.45 However, there is no direct evidence on aggrecanase induction by FN-f in chondrocytes. In contrast to aggrecanase-derived neoepitope, levels of MMP-derived DIPEN341 neoepitope are unchanged in the FN-f-treated cartilage.44
Type-II collagen degradation by fibronectin fragments
Matrix metalloproteinases are a family of zinc-dependent enzymes that mediate the turnover of extracellular matrix proteins. Upregulation of MMPs has been implicated in numerous pathologic processes, including OA and RA. The MMP family is classified into gelatinases, which degrade type-IV collagen and other basement membrane proteins; collagenases, which degrade the stromal fibrillar collagens (types I, II, and III); and others, which degrade additional matrix components.46 Of MMPs, collagenases are particularly important because of their ability to cleave fibrillar collagen, the most abundant component of the extracellular matrix.47 MMP-1 (collagenase-1) is expressed ubiquitously and is found in various cells, including fibroblasts, chondrocytes, and multiple tumor cells.47 MMP-8 (collagenase-2) is expressed mainly in neutrophils.47 MMP-13 (collagenase-3) exhibits the broadest substrate specificity of the collagenases, with the highest activity against type-II collagen, the main collagen in cartilage.48,49 Furthermore, MMP-13 degrades types I, III, IV, X, and XIV collagen, fibronectin, and aggrecan core protein.50–52 While MMP-13 expression is restricted to bone development and bone maintenance under normal physiologic conditions,53,54 it is upregulated under pathologic conditions like in OA chondrocytes, rheumatoid synovium, and tumor cells.55–57 MMP-2 and MMP-9 are widely expressed and are best known as gelatinases.
Werb et al. demonstrated for the first time that treatment of cultured rabbit synovial fibroblasts with the central cellbinding FN-f stimulates expression of MMP-1 and MMP-3.58 The FN-f can induce MMP-13 in human chondrocytes.59 NH2-terminal gelatin-binding FN-f stimulates production of MMP-13 and MMP-3 in porcine chondrocytes.44 NH2-terminal heparin-binding FN-f enhances MMP-3 and gelatinase expressions.36,60 While treatment with COOH-terminal heparin-binding FN-f results in increased production of MMP-3 and MMP-13 in bovine cartilage,37 the FN-f stimulates production of MMP-1, MMP-2, MMP-9, and MMP-13 in human cartilage.61 The COOH-terminal heparin-binding FN-f also induces MMP-1, MMP-3, and MMP-13 in RA synovial fibroblasts.62 In association with MMP production, the immunoassay for detection of type-II collagen cleavage by collagenase55 has demonstrated that COOH-terminal heparin-binding FN-f enhances collagenase-mediated cleavage of type-II collagen in human61 and bovine37 cartilages. Matrix metalloproteinase-13 is a candidate collagenase responsible for the cleavage of type-II collagen because MMP-13 inhibitor can suppress the FN-f-induced collagen cleavage.37
Nitric oxide production by fibronectin fragments
Nitric oxide (NO) is a short-lived free radical that is synthesized enzymatically from l-arginine by a family of NO synthase (NOS) isoenzymes.63,64 Nitric oxide is produced by a variety of cells, including chondrocytes.65 Inducible NOS (iNOS) is expressed in response to bacterial endotoxin and proinflammatory cytokines such as IL-1. Once synthesized, iNOS generates large amounts of NO. Inducible NOS is strongly expressed in synovium and cartilage of patients with inflammatory joint diseases.66 NO acts principally as a proinflammatory and destructive mediator. The pathogenetic role of NO in arthritis is certainly supported by the observation that inhibitors of NOS can suppress the development of disease in animal models, such as adjuvant arthritis and streptococcal cell wall arthritis.67,68 Of FN-fs, NH2-terminal heparin-binding FN-f has been shown to stimulate NO production in association with iNOS induction in human normal chondrocyte monolayer cultures.69 Another FN-f, COOH-terminal heparin-binding FN-f, also causes increased NO production in RA cartilage.70
Cytokine production by fibronectin fragments
The early phase of cartilage degradation is associated with enhanced release of proinflammatory cytokines.71,72 In human cartilage NH2-terminal heparin-binding FN-f stimulates a pulsed release of TNFα and IL-1β, followed by a decrease in a few days. Enhanced release of IL-6 occurs earlier and continues for three weeks. IL-1α release shows a lag period.
Although cell responses to FN-fs and proinflammatory cytokines including IL-1 are qualitatively similar,71,73 the involvement of cytokines in FN-f effects is controversial. The cytokine release by FN-f could partly account for the catabolic effects of NH2-terminal heparin-binding FN-f on MMP-3 production and proteoglycan synthesis in human cartilage because antibodies to these cytokines partially block the FN-f activities.72 Inhibition of FN-f effects with IL-1 receptor antagonist indicates that IL-1 could mediate type-II collagen cleavage by collagenase stimulated with COOH-terminal heparin-binding FN-f in bovine cartilage37 and MMP-3 synthesis enhanced by RGD-containing peptide of central cell-binding FN-f in rabbit chondrocytes.74 In contrast, MMP induction by NH2-terminal gelatin-binding FN-f in porcine chondrocytes44 and by COOH-terminal heparin-binding FN-f in RA synovial fibroblasts62 is not via an IL-1 autocrine loop. Nitric oxide production by NH2-terminal heparin-binding FN-f in human chondrocytes is also IL-1-independent.69
Receptors for fibronectin fragments
Cell-matrix interactions control cell function and behavior by signal transduction through a variety of cell surface receptors. FN can bind several integrins and other cell surface protein ligands.75
Integrin
Integrins are heterodimeric transmembrane proteins consisting of α and β subunits. Integrins bind extracellular matrix molecules and mediate cell adhesion, migration, and invasion during development, tissue repair, tumor invasion, and metastasis. In concert with growth factor or cytokine receptors, integrins regulate cell proliferation, differentiation, and survival.76,77 Integrins also serve as cell surface receptors that transduce intracellular signals.78–80 Although the cytoplasmic domains of the integrin α and β subunits have no intrinsic enzymatic activity, integrin signaling is achieved by coupling signaling molecules to the cytoplasmic and transmembrane domains of the integrin subunits.81 Integrins activate signaling pathways that are either common to all integrins or heterodimer-specific.82 The cytoplasmic domains of α subunits may trigger signaling events that are specific for each individual integrin heterodimers.83,84
There is evidence that integrin regulates FN-f action. FN can bind α5β1 integrin through the cell-binding domain in III10 via RGD sequence (Fig. 1).85,86 Matrix matalloproteinase production by the central cell-binding FN-f is probably mediated by α5β1 integrin because anti-α5β1 integrin antibody and RGD-containing peptide induce MMP-1 and gelatinase in rabbit synovial fibroblasts.58 The cell-binding FN-f and anti-α5β1 integrin antibody can increase MMP-13 production in human chondrocytes.59 Recent studies using antisense oligonucleotides to α5 integrin subunit have also shown the involvement of α5 integrin in cartilage proteoglycan degradation induced by NH2-terminal heparin-binding and NH2-terminal gelatin-binding FN-fs without cell-binding RGD sequence in addition to the central cell-binding FN-f.87 These two NH2-terminal FN-fs can be chemically cross-linked to α5 integrin subunit in chondrocytes.88 However, employment of α5β1 integrin by NH2-terminal heparin-binding FN-f remains to be investigated because blocking antibodies to α5 or β1 integrin subunit fail to inhibit the FN-f-stimulated NO production.69 Integrin α5β1 is the primary receptor involved in the assembly of dimeric fibronectin into the extracellular matrix.89 The I1-5 repeats of NH2-terminal heparin-binding FN-f block the assembly of FN into fibrils, and FN dimers lacking these domains fail to be incorporated into fibrils.90–93 NH2-terminal heparin-binding FN-f may interfere with FN assembly and indirectly alter α5β1 signaling.
Rheumatoid arthritis synovial fibroblasts at the cartilage-pannus junction express integrin subunits α4, α5, and β1.94 Integrin α4β1 recognizes CS-1 in alternatively spliced IIICS domain of FN.95,96 Inhibition of MMP production with anti-α4 integrin antibody indicates that COOH-terminal heparin-binding FN-f, which contains CS-1 (Fig. 1), stimulates MMP-1, MMP-3, and MMP-13 in RA synovial fibroblasts via α4β1 integrin.62 Indeed, CS-1 peptide induces these MMPs in the cells.62 Since α4β1 integrin is newly expressed on articular chondrocytes in OA cartilage,97,98 the COOH-terminal heparin-binding FN-f may work via the integrin in OA chondrocytes.
Excessive amounts of RGD peptide are required to induce proteoglycan release in cartilage explant culture while the central cell-binding FN-f at the same level causes stronger release of proteoglycan.36 Compared with CS-1 peptide, the COOH-terminal heparin-binding FN-f can induce greater levels of MMPs.62 Thus, FN-f could activate integrins more effectively than synthetic peptides.
CD44
Another cell surface receptor that could mediate FN-f action is CD44, a principal hyaluronan receptor.99 The CD44 gene has 20 exons, 12 of which may be alternatively spliced to produce a number of different isoforms.100 Restricted expression of CD44 isoforms and post-translational glycosylation of the parent protein provide diverse functions of CD44. Of CD44 isoforms, CD44H is commonly expressed in human articular chondrocytes.101 Although CD44H is predominant, mRNA containing V3 exon of CD44 is also found in chondrocytes.101 The diversity of CD44 is further amplified by the differential use of glycosaminoglycan attachment sites on its extracellular domain. While chondroitin sulfate proteoglycan is attached to the membrane proximal portion of external domain of CD44H,102 heparan sulfate proteoglycan can bind CD44 at V3 in the membrane proximal extracellular domain of CD44v.103 Chondroitin sulfate and heparan sulfate proteoglycans employ identical or overlapping binding sites in the repeats III13 and III14 of COOH-terminal heparinbinding FN-f (Fig. 1).104,105 The COOH-terminal heparinbinding domain of FN is known to bind CD44.104 While MMP production is up-regulated by COOH-terminal heparin-binding FN-f in human articular cartilage, anti-CD44 antibody can block the enhanced MMP production.61 Suppression of the FN-f-stimulated MMP production by peptide V61 suggests that the peptide V domain, a binding site of COOH-terminal heparin-binding FN-f for cell surface heparan sulfate proteoglycan,106 is required for the FN-f-activated MMP induction. Thus, COOH-terminal heparinbinding FN-f may directly bind glycosaminoglycans on CD44 through the peptide V sequence, resulting in MMP induction.
CD44 is upregulated in articular cartilage from patients with OA107 and RA.108 Compared with normal cartilage, RA cartilage produces higher NO in response to the COOH-terminal heparin-binding FN-f.70 Anti-CD44 treatment using the monoclonal anti-CD44 antibody and the peptide V reveals that NO production enhanced by COOH-terminal heparin-binding FN-f is mediated by CD44 in RA cartilage.70 The inhibitory effects of anti-CD44 treatment are stronger in RA cartilage than in normal one, probably because CD44 is upregulated in RA cartilage and the proportion of CD44-positive chondrocytes is significantly higher than that in normal cartilage.70 These findings indicate that increased NO production by COOH-terminal heparinbinding FN-f in RA cartilage is associated with elevated levels of CD44 on chondrocytes under such pathologic conditions. Of interest, FN-fs themselves may upregulate CD44 on chondrocytes because NH2-terminal heparin-binding FN-f enhances CD44 expression in chondrocytes cultured in alginate beads,109 which allows abundant cartilage matrix deposition around chondrocytes like in vivo cartilage.110
Intracellular signaling pathways activated by fibronectin fragments
Some FN-fs have been shown to activate the intracellular signaling pathways, mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB pathways, leading to cartilage destruction.
Mitogen-activated protein kinase pathway
Activator protein-1 (AP-1), which includes members of the Jun and Fos families, is a pivotal transcriptional factor that regulates the production of cytokines and MMPs. The upstream regulatory regions of MMP genes contain the AP-1 recognition site.111,112 Activator protein-1 can be activated by protein kinases that phosphorylate specific amino acid residues, especially by MAPK families.113 Three major MAPK families have been identified: extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun NH2-terminal kinase (JNK).114,115 All the three MAPK pathways are involved in the transcriptional regulation of Fos and Jun family genes.
The central cell-binding FN-f activates ERK, p38, and JNK, and increases the production of MMP-13 and gelatinases by human articular chondrocytes.59 Another fibronectin fragment, NH2-terminal heparin-binding FN-f, stimulates NO production in association with the activation of ERK, p38, and JNK in human chondrocytes.69 Furthermore, collagenase induction leading to type-II collagen breakdown by COOH-terminal heparin-binding FN-f involves all the three MAPK pathways in human articular cartilage.116 The COOH-terminal heparin-binding FN-f also causes phosphorylation of ERK1/2, JNK, and p38 for MMP production in RA synovial fibroblasts62 and in human natural killer cells.117
Individual MAPK pathways may play different roles in the production of individual MMPs in response to FN-f. In RA synovial fibroblasts ERK seems to be involved in MMP-1, MMP-3, and MMP-13 production with COOH-terminal heparin-binding FN-f stimulation, whereas p38 MAPK may contribute to MMP-3 induction by the FN-f. JNK seems to promote the production of MMP-1 and MMP-13 in the FN-f-stimulated RA synovial fibroblasts.62
Different fragments of fibronectin may activate different isoforms of JNK. In human normal chondrocytes, NH2-terminal heparin-, central cell-, and COOH-terminal heparin-binding FN-fs have been shown to individually activate ERK1/2 and p38.59,69 The NH2-terminal heparin-binding FN-f activates JNK169 whereas the central cell-binding fragment induces the activation of JNK1/2.59 In contrast, the COOH-terminal heparin-binding FN-f activates JNK2.116
Coupling of integrin receptors to MAPK pathways has been reported.118 Anti-α5β1 integrin antibody can activate ERK, p38, and JNK1/2 in human chondrocytes.59 In addition, CS-1 peptide, which binds α5β1 integrin, causes the phosphorylation of these three MAPKs in RA synovial fibroblasts.62 Thus, some integrin-binding FN-fs may employ integrin as a signaling receptor for MAPK activation. Upstream events in activation of MAPK cascades in association with FN-f stimulation remain to be clarified.
Nuclear factor-κB pathway
Nuclear factor-κB is another key regulator for MMPs.119,120 Activation of NF-κB is dependent on the phosphorylation and degradation of IκB, an endogenous inhibitor that binds to NF-κB in the cytoplasm.121 The released NF-κB then translocates to the nucleus, where it binds to specific NF-κB DNA binding sites and initiates gene expression including MMPs.
In contrast to MAPKs, NF-κB activation by FN-fs has rarely been studied. Phosphorylation of IκB by anti-α5β1 antibody suggests that the integrin-binding FN-fs could activate the NF-κB pathway.59 Our preliminary study using NF-κB inhibitor showed that NF-κB could be involved in collagenase production and type-II collagen cleavage by collagenase in human cartilage with treatment with COOHterminal heparin-binding FN-f (Fig. 2). Further investigations will be required to clarify the involvement of NF-κB in catabolic actions of FN-fs.
Other degradation products of cartilage
Other fragments of matrix component can affect chondrocyte metabolism. For instance, fibrillar collagens and their degradation products influence cell-mediated proteolysis. Native and denatured forms of type-II collagen stimulate interstitial collagenase production by skin fibroblast.122 Human monocytes produce elevated levels of IL-1 when exposed to native type-II collagen.123,124 Synovial fluid mononuclear cells from patients with RA produce cytokines such as IL-1, IL-6, and TNFα in response to exposure to type-II collagen.125 The CB11 peptide of type-II collagen can stimulate increased IL-1 production by monocytes/macrophages.126 Jennings et al. have shown that mixed cleavage products of type-II collagen and those extracted from articular cartilage could induce proteolytic cartilage resorption at the level of proteoglycan degradation, and inhibit matrix synthesis.127 Cyanogen bromide-cleaved fragments of type-II collagen can cause increased cleavage of type-II collagen by collagenase in chondrocyte pellet cultures.128 Furthermore, hyaluronan hexasaccharides induce proteoglycan loss, suppression of proteoglycan synthesis, decreased aggregation of aggrecan, and gelatinase activity.129 Hyaluronan fragments also stimulate NO production through iNOS activation in articular chondrocytes.130
Conclusion
Increased fragments from matrix degradation could play an important role in cartilage destruction in arthritis. These fragments activate chondrocytes and synovial fibroblasts, leading to the induction of MMPs, NO, and cytokines. Catabolic activities by FN-fs are probably mediated by cell surface receptors such as integrins that can stimulate catabolic intracellular signals, including MAPK (Fig. 3). Thorough understanding of the mechanism driven by matrix degradation products may contribute to prevention of cartilage destruction in OA and RA.
References
AR Poole (2001) Cartilage in health and disease WJ Koopman (Eds) Arthritis and allied conditions: a textbook of rheumatology, 14th ed. vol 1 Lippincott, Williams and Wilkins Baltimore 226–84
DR Eyre (1987) ArticleTitleCollagen cross-linking amino acids Methods Enzymol 144 115–39 Occurrence Handle3626870 Occurrence Handle10.1016/0076-6879(87)44176-1 Occurrence Handle1:CAS:528:DyaL1cXhsVKnsbs%3D
GE Kempson H Muir C Pollard M Tuke (1973) ArticleTitleThe tensile properties of the cartilage of human femoral condyles related to the content of collagen and glycosaminoglycans Biochim Biophys Acta 297 456–72 Occurrence Handle4267503 Occurrence Handle1:CAS:528:DyaE3sXht1Sls7s%3D
Mow VC, Setton LA, Ratcliffe DS, Howell DS, Buckwalter JA. Structure-function relationships of articular cartilage and the effects of joint instability and trauma on cartilage function. In: Brandt KD, editor. Cartilage changes in osteoarthritis. Indiana School of Medicine/CibaGeigy; 1990. 22–42
SL Carney MEJ Billingham H Muir JD Sandy (1984) ArticleTitleDemonstration of increased proteoglycan turnover in cartilage explants from dogs with experimental osteoarthritis J Orthop Res 2 201–6 10.1002/jor.1100020301 Occurrence Handle6491812 Occurrence Handle10.1002/jor.1100020301 Occurrence Handle1:CAS:528:DyaL2MXit1ersw%3D%3D
CA McDevitt H Muir (1976) ArticleTitleBiochemical changes in the cartilage of the knee in experimental and natural osteoarthritis in the dog J Bone Joint Surg [Br] 58 94–101 Occurrence Handle1:STN:280:DyaE287ptVantA%3D%3D
LJ Bonassar EH Frank JC Murray CG Paguio VL Moore MW Lark et al. (1995) ArticleTitleChanges in cartilage composition and physical properties due to stromelysin degradation Arthritis Rheum 38 173–83 Occurrence Handle7848307 Occurrence Handle10.1002/art.1780380205 Occurrence Handle1:STN:280:DyaK2M7ltFSntw%3D%3D
GE Kempson (1979) Mechanical properties of articular cartilage MAR Freeman (Eds) Adult articular cartilage Pitman Medical Tunbridge Wells 333–414
G Dodge AR Poole (1989) ArticleTitleImmunohistochemical detection and immunohistochemical analysis of type II collagen degradation in human normal, rheumatoid and osteoarthritic articular cartilages and in explants of bovine articular cartilage cultured with interleukin-1 J Clin Invest 83 647–61 Occurrence Handle2783591 Occurrence Handle10.1172/JCI113929 Occurrence Handle1:CAS:528:DyaL1MXhtFaltrw%3D
AP Hollander I Pidoux A Reiner C Rorabeck R Bourne AR Poole (1994) ArticleTitleIncreased damage to type II collagen in osteoarthritic articular cartilage detected by a new immunoassay J Clin Invest 93 1722–32 Occurrence Handle7512992 Occurrence Handle10.1172/JCI117156 Occurrence Handle1:CAS:528:DyaK2cXivFGqsrc%3D
WP Arend JM Dayer (1995) ArticleTitleInhibition of the production and effects of interleukin-1 and tumor necrosis factor alpha in rheumatoid arthritis Arthritis Rheum 38 151–60 Occurrence Handle7848304 Occurrence Handle10.1002/art.1780380202 Occurrence Handle1:STN:280:DyaK2M7ltFSnsA%3D%3D
N Burton-Wurster M Butler S Harter C Colombo J Quintavalla D Swartzendurber et al. (1986) ArticleTitlePresence of fibronectin in articular cartilage in two animal models of osteoarthritis J Rheumatol 13 175–82 Occurrence Handle3701731 Occurrence Handle1:CAS:528:DyaL28XitVCqsbc%3D
BB Lavietes S Carsons HS Diamond RS Laskin (1985) ArticleTitleSynthesis, secretion, and deposition of fibronectin in cultured human synovium Arthritis Rheum 28 1016–26 Occurrence Handle4038355 Occurrence Handle10.1002/art.1780280909 Occurrence Handle1:STN:280:DyaL2MzgslWhsQ%3D%3D
RO Hynes (1990) Fibronectins Springer Berlin Heidelberg New York
JE Schwarzbauer (1991) ArticleTitleAlternative splicing of fibronectin: three variants, three functions BioEssays 13 527–33 10.1002/bies.950131006 Occurrence Handle1755828 Occurrence Handle10.1002/bies.950131006 Occurrence Handle1:CAS:528:DyaK38XitlGk
E Ruoslahti (1988) ArticleTitleFibronectin and its receptors Annu Rev Biochem 57 375–413 10.1146/annurev.bi.57.070188.002111 Occurrence Handle2972252 Occurrence Handle10.1146/annurev.bi.57.070188.002111 Occurrence Handle1:CAS:528:DyaL1cXlt1Cnt7Y%3D
KM Yamada (1991) ArticleTitleAdhesive recognition sequences J Biol Chem 266 12809–12 Occurrence Handle2071570 Occurrence Handle1:CAS:528:DyaK3MXks1yquro%3D
JB McCarthy MK Chelberg DJ Mickelson LT Furcht (1988) ArticleTitleLocalization and chemical synthesis of fibronectin peptides with melanoma adhesion and heparin binding activities Biochemistry 27 1380–8 10.1021/bi00404a044 Occurrence Handle2966638 Occurrence Handle10.1021/bi00404a044 Occurrence Handle1:CAS:528:DyaL1cXpt1eqsQ%3D%3D
SL Drake DJ Klein DJ Mickelson TR Oegema LT Furcht JB McCarthy (1992) ArticleTitleCell surface phosphatidylinositol-anchored heparan sulfate proteoglycan initiates mouse melanoma cell adhesion to a fibronectin-derived, heparin-binding synthetic peptide J Cell Biol 117 1331–41 10.1083/jcb.117.6.1331 Occurrence Handle1607392 Occurrence Handle10.1083/jcb.117.6.1331 Occurrence Handle1:CAS:528:DyaK38Xitlaqtbc%3D
J Iida AP Skubitz LT Furcht EW Wayner JB McCarthy (1992) ArticleTitleCoordinate role for cell surface chondroitin sulfate proteoglycan and α4β1 in mediating melanoma cell adhesion to fibronectin J Cell Biol 118 431–44 10.1083/jcb.118.2.431 Occurrence Handle1629241 Occurrence Handle10.1083/jcb.118.2.431 Occurrence Handle1:CAS:528:DyaK38Xlt12jsb4%3D
V Lories JJ Cassiman H van der Berghe G David (1992) ArticleTitleDifferential expression of cell surface heparan sulfate proteoglycans in human mammary epithelial cell and fibroblasts J Biol Chem 267 1116–22 Occurrence Handle1339431 Occurrence Handle1:CAS:528:DyaK38XjvVCjug%3D%3D
A Woods JB McCarthy LT Furcht JR Couchman (1993) ArticleTitleA synthetic peptide from the COOH-terminal heparin-binding domain of fibronectin promotes focal adhesion formation Mol Biol Cell 4 605–13 Occurrence Handle8374170 Occurrence Handle1:CAS:528:DyaK3sXmt1altLY%3D
JM Giuseppetti JB McCarthy PC Letourneau (1994) ArticleTitleIsolation and partial characterization of a cell-surface heparan sulfate proteoglycan from embryonic rat spinal cord J Neurosci Res 37 584–95 10.1002/jnr.490370505 Occurrence Handle8028039 Occurrence Handle10.1002/jnr.490370505 Occurrence Handle1:CAS:528:DyaK2cXis1Kmurw%3D
EA Wayner A Garcia-Pardo MJ Humphries JA McDonald WG Carter (1989) ArticleTitleIdentification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin J Cell Biol 109 1321–30 10.1083/jcb.109.3.1321 Occurrence Handle2527858 Occurrence Handle10.1083/jcb.109.3.1321 Occurrence Handle1:CAS:528:DyaL1MXlslajtLc%3D
J-L Guan RO Hynes (1990) ArticleTitleLymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor α4β1 Cell 60 53–61 10.1016/0092-8674(90)90715-Q Occurrence Handle2295088 Occurrence Handle10.1016/0092-8674(90)90715-Q Occurrence Handle1:CAS:528:DyaK3cXhslKisr8%3D
AP Mould MJ Humphries (1991) ArticleTitleIdentification of a novel recognition sequence for the α4β1 in the COOH-terminal heparin-binding domain of fibronectin EMBO J 10 4089–95 Occurrence Handle1756719 Occurrence Handle1:CAS:528:DyaK38XhtVWgsbY%3D
AP Mould LA Wheldon A Koriyama EA Wayner KM Yamada MJ Humphries (1990) ArticleTitleAffinity chromatographic isolation of the melanoma adhesion receptor for the IIICS region of fibronectin recognized by the integrin α4β1 J Biol Chem 265 4020–4 Occurrence Handle2137460 Occurrence Handle1:CAS:528:DyaK3cXhvFCjsr0%3D
AP Mould A Koriyama KM Yamada MJ Humphries (1991) ArticleTitleThe CS5 peptide is a second site in the IIICS region of fibronectin recognized by the integrin α4β1 J Biol Chem 266 3579–85 Occurrence Handle1750929 Occurrence Handle1:CAS:528:DyaK3MXitVWqtL4%3D
DR Miller HJ Mankin H Shoji RD D’Ambrosia (1984) ArticleTitleIdentification of fibronectin in preparations of osteoarthritic human cartilage Connect Tissue Res 12 267–75 Occurrence Handle6478826 Occurrence Handle10.3109/03008208409013689 Occurrence Handle1:CAS:528:DyaL2cXkslSntrs%3D
KL Jones M Brown SY Ali RA Brown (1987) ArticleTitleAn immunohistochemical study of fibronectin in human osteoarthritic and disease-free articular cartilage Ann Rheum Dis 46 809–15 Occurrence Handle3322211 Occurrence Handle10.1136/ard.46.11.809 Occurrence Handle1:STN:280:DyaL1c7gsFGqsw%3D%3D
GA Homandberg C Wen F Hui (1998) ArticleTitleCartilage damaging activities of fibronectin fragments derived from cartilage and synovial fluid Osteoarthritis Cartilage 6 231–44 10.1053/joca.1998.0116 Occurrence Handle9876392 Occurrence Handle10.1053/joca.1998.0116 Occurrence Handle1:STN:280:DyaK1M%2FptlKksA%3D%3D
DL Xie R Meyers GA Homandberg (1992) ArticleTitleFibronectin fragments in osteoarthritic synovial fluid J Rheumatol 19 1448–52 Occurrence Handle1433014 Occurrence Handle1:STN:280:DyaK3s%2FlvFSiuw%3D%3D
DL Scott JP Delamare KW Walton (1981) ArticleTitleThe distribution of fibronectin in the pannus in rheumatoid arthritis Br J Exp Pathol 62 362–68 Occurrence Handle7028072 Occurrence Handle1:STN:280:DyaL38%2Fks1ansA%3D%3D
S Shiozawa M Ziff (1983) ArticleTitleImmunoelectron microscopic demonstration of fibronectin in rheumatoid pannus and at the cartilage-pannus junction Ann Rheum Dis 42 254–63 Occurrence Handle6344809 Occurrence Handle10.1136/ard.42.3.254 Occurrence Handle1:STN:280:DyaL3s3ivFyguw%3D%3D
DL Xie GA Homandberg (1993) ArticleTitleFibronectin fragments bind to and penetrate cartilage tissue resulting in proteinase expression and cartilage damage Biochim Biophys Acta 1182 189–96 Occurrence Handle8357850 Occurrence Handle1:CAS:528:DyaK3sXms1yjtr8%3D
GA Homandberg R Meyers DL Xie (1992) ArticleTitleFibronectin fragments cause chondrolysis of bovine articular cartilage slices in culture J Biol Chem 267 3597–604 Occurrence Handle1740411 Occurrence Handle1:CAS:528:DyaK38XhsVyrurY%3D
T Yasuda AR Poole (2002) ArticleTitleA fibronectin fragment induces type II collagen degradation by collagenase through an interleukin-1-mediated pathway Arthritis Rheum 46 138–48 10.1002/1529-0131(200201)46:1<138::AID-ART10051>3.0.CO;2-K Occurrence Handle11817586 Occurrence Handle10.1002/1529-0131(200201)46:1<138::AID-ART10051>3.0.CO;2-K Occurrence Handle1:CAS:528:DC%2BD38Xht1Wlu7g%3D
GA Homandberg R Meyers JM Williams (1993) ArticleTitleIntraarticular injection of fibronectin fragments causes severe depletion of cartilage proteoglycans in vivo J Rheumatol 20 1378–82 Occurrence Handle8230023 Occurrence Handle1:STN:280:DyaK2c%2Fks1ylsw%3D%3D
DL Xie F Hui GA Homandberg (1993) ArticleTitleFibronectin fragments alter matrix protein synthesis in cartilage tissue cultured in vitro Arch Biochem Biophys 307 110–8 10.1006/abbi.1993.1568 Occurrence Handle8239647 Occurrence Handle10.1006/abbi.1993.1568 Occurrence Handle1:CAS:528:DyaK3sXms1OlsrY%3D
I Abbaszade RQ Liu F Yang SA Rosenfeld OH Ross JR Link et al. (1999) ArticleTitleCloning and characterization of ADAMTS11, an aggrecanase from ADAMTS family J Biol Chem 274 23443–50 10.1074/jbc.274.33.23443 Occurrence Handle10438522 Occurrence Handle10.1074/jbc.274.33.23443 Occurrence Handle1:CAS:528:DyaK1MXltlKnu74%3D
MD Tortorella TC Burn MA Pratta I Abbaszade JM Hollos R Liu et al. (1999) ArticleTitlePurification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins Science 284 1664–6 10.1126/science.284.5420.1664 Occurrence Handle10356395 Occurrence Handle10.1126/science.284.5420.1664 Occurrence Handle1:CAS:528:DyaK1MXjs1KitL0%3D
AJ Fosang (1999) Aggrecanase and cartilage proteoglycan degradation D Bradshaw JS Nixon K Bottomley (Eds) Metalloproteinases as targets for anti-inflammatory drugs Birkhauser Basel 117–43
II Singer S Scott DW Kawka EK Bayne JR Weidner HR Williams et al. (1997) ArticleTitleAggrecan degradation in human cartilage. Evidence for both matrix metalloproteinase and aggrecanase activity in normal, osteoarthritic, and rheumatoid joints J Clin Invest 100 93–106 Occurrence Handle9202061 Occurrence Handle10.1172/JCI119526
H Stanton L Ung AJ Fosang (2002) ArticleTitleThe 45 kDa collagen-binding fragment of fibronectin induces matrix metalloproteinase-13 synthesis by chondrocytes and aggrecan degradation by aggrecanases Biochem J 364 181–90 Occurrence Handle11988091 Occurrence Handle1:CAS:528:DC%2BD38XktFWhsrs%3D
GA Homandberg G Davis C Maniglia A Shrikhande (1997) ArticleTitleCartilage chondrolysis by fibronectin fragments causes cleavage of aggrecan at the same site as found in osteoarthritic cartilage Osteoarthritis Cartilage 5 450–3 10.1016/S1063-4584(97)80049-0 Occurrence Handle9536293 Occurrence Handle10.1016/S1063-4584(97)80049-0 Occurrence Handle1:STN:280:DyaK1c7pslemtA%3D%3D
H Nagase JF Woessner SuffixJr (1999) ArticleTitleMatrix metalloproteinases J Biol Chem 274 21491–4 10.1074/jbc.274.31.21491 Occurrence Handle10419448 Occurrence Handle10.1074/jbc.274.31.21491 Occurrence Handle1:CAS:528:DyaK1MXltVynu7s%3D
J Jeffery (1998) Interstitial collagenases WC Parks RP Mecham (Eds) Matrix metalloproteinases Academic Press San Diego 15–38 Occurrence Handle10.1016/B978-012545090-4/50003-3
JM Freije I Diez-Itza B Balbín LM Sanchez R Blasco J Tolivia et al. (1994) ArticleTitleMolecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas J Biol Chem 269 16766–73 Occurrence Handle8207000 Occurrence Handle1:CAS:528:DyaK2cXltlWisL0%3D
V Knäuper S Cowell B Smith C López-Otín M O’Shea H Morris et al. (1997) ArticleTitleThe role of the C-terminal domain of human collagenase-3 (MMP-13) in the activation of procollagenase-3, substrate specificity, and tissue inhibitor of metalloproteinase interaction J Biol Chem 272 7608–16 10.1074/jbc.272.12.7608 Occurrence Handle9065415 Occurrence Handle10.1074/jbc.272.7.4281
SM Krane MH Byrne V Lemaitre P Henriet JJ Jeffrey JP Witter et al. (1996) ArticleTitleDifferent collagenase gene products have different roles in degradation of type I collagen J Biol Chem 271 28509–15 10.1074/jbc.271.45.28509 Occurrence Handle8910479 Occurrence Handle10.1074/jbc.271.45.28509 Occurrence Handle1:CAS:528:DyaK28XmvVegtb0%3D
AJ Fosang K Last V Knäuper G Murphy PJ Neame (1996) ArticleTitleDegradation of cartilage aggrecan by collagenase-3 (MMP-13) FEBS Lett 380 17–20 10.1016/0014-5793(95)01539-6 Occurrence Handle8603731 Occurrence Handle10.1016/0014-5793(95)01539-6 Occurrence Handle1:CAS:528:DyaK28XhsValsLY%3D
V Knäuper C López-Otín B Smith G Knight G Murphy (1996) ArticleTitleBiochemical characterization of human collagenase-3 J Biol Chem 271 1544–50 10.1074/jbc.271.3.1544 Occurrence Handle8576151 Occurrence Handle10.1074/jbc.271.3.1544
M Stahle-Backdahl B Sandstedt K Bruce A Lindahl MG Jiménez JA Vega et al. (1997) ArticleTitleCollagenase-3 (MMP-13) is expressed during human fetal ossification and re-expressed in postnatal bone remodeling and in rheumatoid arthritis Lab Invest 76 717–28 Occurrence Handle9166290 Occurrence Handle1:STN:280:DyaK2szgvFSquw%3D%3D
N Johansson U Saarialho-Kere K Airola R Herva L Nissinen J Westermarck et al. (1997) ArticleTitlecollagenase-3 (MMP-13) is expressed by hypertrophic chondrocytes, periosteal cells, and osteoblasts during human fetal bone development Dev Dyn 208 387–97 10.1002/(SICI)1097-0177(199703)208:3<387::AID-AJA9>3.0.CO;2-E Occurrence Handle9056642 Occurrence Handle10.1002/(SICI)1097-0177(199703)208:3<387::AID-AJA9>3.0.CO;2-E Occurrence Handle1:CAS:528:DyaK2sXit1GqtL8%3D
RC Billinghurst L Dahlberg M Ionescu A Reiner R Bourne C Rorabeck et al. (1997) ArticleTitleEnhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage J Clin Invest 99 1534–45 Occurrence Handle9119997 Occurrence Handle10.1172/JCI119316 Occurrence Handle1:CAS:528:DyaK2sXitlantL0%3D
O Lindy YT Konttinen T Sorsa Y Ding S Santavirta A Ceponis (1997) ArticleTitleMatrix metalloproteinase 13 (collagenase 3) in human rheumatoid synovium Arthritis Rheum 40 1391–9 Occurrence Handle9259418 Occurrence Handle10.1002/art.1780400806 Occurrence Handle1:CAS:528:DyaK2sXls1Okt7k%3D
M Balbín AM Pendás JA Uría MG Jiménez JP Freije C López-Otín (1999) ArticleTitleExpression and regulation of collagenase-3 (MMP-13) in human malignant tumors APMIS 107 45–53 Occurrence Handle10190279 Occurrence Handle10.1111/j.1699-0463.1999.tb01525.x
Z Werb PM Tremble O Behrendtsen E Crowley CH Damsky (1989) ArticleTitleSignal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression J Cell Biol 109 877–89 10.1083/jcb.109.2.877 Occurrence Handle2547805 Occurrence Handle10.1083/jcb.109.2.877 Occurrence Handle1:CAS:528:DyaL1MXltFalt7g%3D
CB Forsyth J Pulai RF Loeser (2002) ArticleTitleFibronectin fragments and blocking antibodies to α2β1 and α5β1 integrins stimulate mitogen-activated protein kinase signaling and increase collagenase 3 (matrix metalloproteinase 13) production by human articular chondrocytes Arthritis Rheum 46 2368–76 10.1002/art.10502 Occurrence Handle12355484 Occurrence Handle10.1002/art.10502 Occurrence Handle1:CAS:528:DC%2BD38XosVGjurw%3D
D-L Xie F Hui R Meyers GA Homandberg (1994) ArticleTitleCartilage chondrolysis by fibronectin fragments is associated with release of several proteinases: stromelysin plays a major role in chondrolysis Arch Biochem Biophys 311 205–12 10.1006/abbi.1994.1228 Occurrence Handle8203882 Occurrence Handle10.1006/abbi.1994.1228 Occurrence Handle1:CAS:528:DyaK2cXktlWqtr0%3D
T Yasuda AR Poole M Shimizu T Nakagawa SM Julovi H Tamamura et al. (2003) ArticleTitleInvolvement of CD44 in induction of matrix metalloproteinases by a carboxyl-terminal heparin-binding fragment of fibronectin in human articular cartilage in culture Arthritis Rheum 48 1271–80 10.1002/art.10951 Occurrence Handle12746900 Occurrence Handle10.1002/art.10951 Occurrence Handle1:CAS:528:DC%2BD3sXkt1aktr4%3D
T Yasuda M Shimizu T Nakagawa SM Julovi T Nakamura (2003) ArticleTitleMatrix metalloproteinase production by COOH-terminal heparin-binding fibronectin fragment in rheumatoid synovial cells Lab Invest 83 153–62 Occurrence Handle12594231 Occurrence Handle1:CAS:528:DC%2BD3sXht1Cmtro%3D
S Moncada A Higgs (1993) ArticleTitleThe L-arginine-nitric oxide pathway N Engl J Med 329 2002–12 10.1056/NEJM199312303292706 Occurrence Handle7504210 Occurrence Handle10.1056/NEJM199312303292706 Occurrence Handle1:CAS:528:DyaK2cXhsF2ntrw%3D
C Nathan (1992) ArticleTitleNitric oxide as a secretory product of mammalian cells FASEB J 6 3051–64 Occurrence Handle1381691 Occurrence Handle1:CAS:528:DyaK38XmtV2ns7o%3D
J Stadler M Stefanovic-Racic TR Billiar RD Curran LA McIntyre HI Georgescu et al. (1991) ArticleTitleArticular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide J Immunol 147 3915–20 Occurrence Handle1658153 Occurrence Handle1:CAS:528:DyaK38XlslSntA%3D%3D
H Sakurai H Kohsaka MF Liu H Higashiyama Y Hirata K Kanno et al. (1995) ArticleTitleNitric oxide production and inducible nitric oxide synthase expression in inflammatory arthritides J Clin Invest 96 2357–63 10.1172/JCI118292 Occurrence Handle7593623 Occurrence Handle10.1172/JCI118292 Occurrence Handle1:CAS:528:DyaK28XltF2hsA%3D%3D
A Ialenti S Moncada M Di Rosa (1993) ArticleTitleModulation of adjuvant arthritis by endogenous nitric oxide Br J Pharmacol 110 701–6 Occurrence Handle8242242 Occurrence Handle1:CAS:528:DyaK2cXmtFyi
N McCartney-Francis JB Allen DE Mizel JE Albina QW Xie CF Nathan et al. (1993) ArticleTitleSuppression of arthritis by an inhibitor of nitric oxide synthase J Exp Med 178 749–54 10.1084/jem.178.2.749 Occurrence Handle7688035 Occurrence Handle10.1084/jem.178.2.749 Occurrence Handle1:CAS:528:DyaK3sXlsFWrsL8%3D
T Gemba J Valbracht S Alsalameh M Lotz (2002) ArticleTitleFocal adhesion kinase and mitogen-activated protein kinases are involved in chondrocyte activation by the 29-kDa amino-terminal fibronectin fragment J Biol Chem 277 907–11 10.1074/jbc.M109690200 Occurrence Handle11677248 Occurrence Handle10.1074/jbc.M109690200 Occurrence Handle1:CAS:528:DC%2BD38XnvFOgsA%3D%3D
T Yasuda T Kakinuma SM Julovi M Yoshida T Hiramitsu M Akiyoshi et al. (2004) ArticleTitleCOOH-terminal heparin-binding fibronectin fragment induces nitric oxide production in rheumatoid cartilage through CD44 Rheumatology (Oxford) 43 1116–20 10.1093/rheumatology/keh274 Occurrence Handle10.1093/rheumatology/keh274 Occurrence Handle1:CAS:528:DC%2BD2cXntFagsbo%3D
GA Homandberg F Hui C Wen (1996) ArticleTitleAssociation of proteoglycan degradation with catabolic cytokine and stromelysin release from cartilage cultured with fibronectin fragments Arch Biochem Biophys 334 325–31 10.1006/abbi.1996.0461 Occurrence Handle8900407 Occurrence Handle10.1006/abbi.1996.0461 Occurrence Handle1:CAS:528:DyaK28Xmt1Smt7s%3D
GA Homandberg F Hui C Wen C Purple K Bewsey H Koepp et al. (1997) ArticleTitleFibronectin-fragment-induced cartilage chondrolysis is associated with release of catabolic cytokines Biochem. J 321 751–7 Occurrence Handle9032463 Occurrence Handle1:CAS:528:DyaK2sXhsVakurs%3D
KE Bewsey C Wen C Purple GA Homandberg (1996) ArticleTitleFibronectin fragments induce the expression of stromelysin-1 mRNA and protein in bovine chondrocytes in monolayer culture Biochim Biophys Acta 1317 55–64 Occurrence Handle8876627
EC Arner MD Tortorella (1995) ArticleTitleSignal transduction through chondrocyte integrin receptors induces matrix metalloproteinase synthesis and synergizes with interleukin-1 Arthritis Rheum 38 1304–14 Occurrence Handle7575726 Occurrence Handle10.1002/art.1780380919 Occurrence Handle1:CAS:528:DyaK2MXpsVSitbo%3D
S Johansson G Svineng K Wennerberg A Armulik L Lohikangas (1997) ArticleTitleFibronectin-integrin interactions Front Biosci 2 D126–46 Occurrence Handle9159220 Occurrence Handle1:CAS:528:DyaK1cXhtVOiurc%3D
RO Hynes (1992) ArticleTitleIntegrins: versatility, modulation, and signaling in cell adhesion Cell 69 11–25 10.1016/0092-8674(92)90115-S Occurrence Handle1555235 Occurrence Handle10.1016/0092-8674(92)90115-S Occurrence Handle1:CAS:528:DyaK38XitFWmtrg%3D
FG Giancotti F Mainiero (1994) ArticleTitleIntegrin-mediated adhesion and signaling in tumorigenesis Biochem Biophys Acta 1198 47–64 Occurrence Handle8199195 Occurrence Handle1:CAS:528:DyaK2cXktlaisrg%3D
EA Clark JS Brugge (1995) ArticleTitleIntegrins and signal transduction pathway: the road taken Science 268 233–9 Occurrence Handle7716514 Occurrence Handle10.1126/science.7716514 Occurrence Handle1:CAS:528:DyaK2MXltVCitLk%3D
MA Schwarz MD Scaller MH Ginsberg (1995) ArticleTitleIntegrins: emerging paradigms of signal transduction Annu Rev Cell Dev Biol 11 549–99 10.1146/annurev.cb.11.110195.003001 Occurrence Handle10.1146/annurev.cb.11.110195.003001
FG Giancotti E Ruoslahti (1999) ArticleTitleIntegrin signaling Science 285 1028–32 10.1126/science.285.5430.1028 Occurrence Handle10446041 Occurrence Handle10.1126/science.285.5430.1028 Occurrence Handle1:CAS:528:DyaK1MXlt1Gns7o%3D
KM Yamada S Miyamoto (1995) ArticleTitleIntegrin transmembrane signaling and cytoskeletal control Curr Opin Cell Biol 7 681–9 10.1016/0955-0674(95)80110-3 Occurrence Handle8573343 Occurrence Handle10.1016/0955-0674(95)80110-3 Occurrence Handle1:CAS:528:DyaK2MXosVKnsrc%3D
FG Giancotti (1997) ArticleTitleIntegrin signaling: specificity and cell cycle progression Curr Opin Cell Biol 9 691–700 10.1016/S0955-0674(97)80123-8 Occurrence Handle9330873 Occurrence Handle10.1016/S0955-0674(97)80123-8 Occurrence Handle1:CAS:528:DyaK2sXmsFCgsbg%3D
Z Zhang K Vuori JC Reed E Ruoslahti (1995) ArticleTitleThe α5β1 integrin supports survival of cells on fibronectin and up-regulates Bcl-2 expression Proc Natl Soc Sci USA 92 6161–5 10.1073/pnas.92.13.6161 Occurrence Handle10.1073/pnas.92.13.6161 Occurrence Handle1:CAS:528:DyaK2MXmsFajs7w%3D
SK Sastry M Lakonishok DA Thomas J Muschler AF Horwitz (1996) ArticleTitleIntegrin α subunit ratios, cytoplasmic domains, and growth factor synergy regulate muscle proliferation and differentiation J Cell Biol 133 169–84 10.1083/jcb.133.1.169 Occurrence Handle8601606 Occurrence Handle10.1083/jcb.133.1.169 Occurrence Handle1:CAS:528:DyaK28XitVChtb4%3D
KM Yamada (1991) ArticleTitleAdhesive recognition sequences J Biol Chem 266 12809–12 Occurrence Handle2071570 Occurrence Handle1:CAS:528:DyaK3MXks1yquro%3D
CH Damsky Z Werb (1992) ArticleTitleSignal transduction by integrin receptors for extracellular matrix: cooperative processing of extracellular information Curr Opin Cell Biol 4 772–81 10.1016/0955-0674(92)90100-Q Occurrence Handle1329869 Occurrence Handle10.1016/0955-0674(92)90100-Q Occurrence Handle1:CAS:528:DyaK3sXjsVCrsw%3D%3D
GA Homandberg V Costa V Ummadi R Pichika (2002) ArticleTitleAntisense oligonucleotides to the integrin receptor subunit alpha5 decrease fibronectin fragment mediated cartilage chondrolysis Osteoarthritis Cartilage 10 381–93 10.1053/joca.2002.0524 Occurrence Handle12027539 Occurrence Handle10.1053/joca.2002.0524 Occurrence Handle1:STN:280:DC%2BD38zjt1Oqtg%3D%3D
GA Homandberg V Costa C Wen (2002) ArticleTitleFibronectin fragments active in chondrocytic chondrolysis can be chemically cross-linked to the alpha5 integrin receptor subunit Osteoarthritis Cartilage 10 938–49 10.1053/joca.2002.0854 Occurrence Handle12464554 Occurrence Handle10.1053/joca.2002.0854 Occurrence Handle1:STN:280:DC%2BD38jgtlektg%3D%3D
BJ Dzamba H Bultmann SK Akiyama DM Peters (1994) ArticleTitleSubstrate-specific binding of the amino terminus of fibronectin to an integrin complex in focal adhesions J Biol Chem 269 19646–52 Occurrence Handle7518462 Occurrence Handle1:CAS:528:DyaK2cXltlSru78%3D
PJ McKeown-Longo DF Mosher (1985) ArticleTitleInteraction of the 70,000-mol-wt amino-terminal fragment of fibronectin with the matrix-assembly receptor of fibroblasts J Cell Biol 100 364–74 10.1083/jcb.100.2.364 Occurrence Handle3155749 Occurrence Handle10.1083/jcb.100.2.364 Occurrence Handle1:CAS:528:DyaL2MXptlGltw%3D%3D
BJ Quade JA McDonald (1988) ArticleTitleFibronectin’s amino-terminal matrix assembly site is located within the 29-kDa amino-terminal domain containing five type I repeats J Biol Chem 263 19602–9 Occurrence Handle2974038 Occurrence Handle1:CAS:528:DyaL1cXmt1Gitrg%3D
JE Schwarzbauer (1991) ArticleTitleIdentification of the fibronectin sequences required for assembly of a fibrillar matrix J Cell Biol 113 1463–73 10.1083/jcb.113.6.1463 Occurrence Handle2045422 Occurrence Handle10.1083/jcb.113.6.1463 Occurrence Handle1:CAS:528:DyaK3MXit1KltLw%3D
J Sottile J Schwarzbauer J Selegue DF Mosher (1991) ArticleTitleFive type I modules of fibronectin form a functional unit that binds to fibroblasts and Staphylococcus aureus J Biol Chem 266 12840–3 Occurrence Handle1677003 Occurrence Handle1:CAS:528:DyaK3MXltVyrt7Y%3D
H Ishikawa S Hirata Y Nishibayashi S Imura H Kubo O Ohno (1994) ArticleTitleThe role of adhesion molecules in synovial pannus formation in rheumatoid arthritis Clin Orthop 300 297–303 Occurrence Handle8131352
EA Wayner A Garcia-Pardo MJ Humphries A McDonald WG Carter (1989) ArticleTitleIdentification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin J Cell Biol 109 1321–30 10.1083/jcb.109.3.1321 Occurrence Handle2527858 Occurrence Handle10.1083/jcb.109.3.1321 Occurrence Handle1:CAS:528:DyaL1MXlslajtLc%3D
J-L Guan RO Hynes (1990) ArticleTitleLymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor α4β1 Cell 60 53–61 10.1016/0092-8674(90)90715-Q Occurrence Handle2295088 Occurrence Handle10.1016/0092-8674(90)90715-Q Occurrence Handle1:CAS:528:DyaK3cXhslKisr8%3D
G Lapadula F Iannoue C Zuccaro V Grattgliano M Covell V Patella et al. (1997) ArticleTitleIntegrin expression on chondrocytes: Correlations with the degree of cartilage damage in human osteoarthritis Clin Exp Rheum 15 247–54 Occurrence Handle1:STN:280:DyaK2szitFWrug%3D%3D
K Ostergaard M Salter J Petersen K Bendtzen J Hvalris CB Andersen (1998) ArticleTitleExpression of α and β subunits of the integrin superfamily in articular cartilage from macroscopically normal and osteoarthritic human femoral heads Ann Rheum Dis 57 303–8 10.1136/ard.57.5.303 Occurrence Handle9741315 Occurrence Handle10.1136/ard.57.5.303 Occurrence Handle1:STN:280:DyaK1cvhtlOmsg%3D%3D
A Aruffo I Stamenkovic M Melnick CB Underhill B Seed (1990) ArticleTitleCD44 is the principal cell surface receptor for hyaluronate Cell 61 1303–13 10.1016/0092-8674(90)90694-A Occurrence Handle1694723 Occurrence Handle10.1016/0092-8674(90)90694-A Occurrence Handle1:CAS:528:DyaK3cXkslGgtbc%3D
GR Screaton MV Bell DG Jackson FB Cornelis U Gerth JI Bell (1992) ArticleTitleGenomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons Proc Natl Acad Sci USA 89 12160–4 10.1073/pnas.89.24.12160 Occurrence Handle1465456 Occurrence Handle10.1073/pnas.89.24.12160 Occurrence Handle1:CAS:528:DyaK3sXhvVCrsLc%3D
DM Salter JL Godolphin MS Gourlay MF Lawson DE Hughs E Dunne (1996) ArticleTitleAnalysis of human articular chondrocyte CD44 isoform expression and function in health and disease J Pathol 179 396–402 10.1002/(SICI)1096-9896(199608)179:4<396::AID-PATH606>3.0.CO;2-G Occurrence Handle8869287 Occurrence Handle10.1002/(SICI)1096-9896(199608)179:4<396::AID-PATH606>3.0.CO;2-G Occurrence Handle1:STN:280:DyaK2s%2Fit12htQ%3D%3D
J Lesley R Hyman (1998) ArticleTitleCD44 structure and function Front Biosci 3 D616–30 Occurrence Handle9634544 Occurrence Handle1:CAS:528:DyaK1cXlvVWisrk%3D
KL Bennet DG Jackson JC Simon E Tanczos R Peach B Modrell et al. (1995) ArticleTitleCD44 isoforms containing exon V3 are responsible for the presentation of heparin-binding growth factor J Cell Biol 128 687–98 10.1083/jcb.128.4.687 Occurrence Handle10.1083/jcb.128.4.687
S Jalkanen M Jalkanen (1992) ArticleTitleLymphocyte CD44 binds the COOH-terminal heparin-binding domain of fibronectin J Cell Biol 116 817–25 10.1083/jcb.116.3.817 Occurrence Handle1730778 Occurrence Handle10.1083/jcb.116.3.817 Occurrence Handle1:CAS:528:DyaK38XotFOitw%3D%3D
FJ Barkalow JE Schwarzbauer (1994) ArticleTitleInteractions between fibronectin and chondroitin sulfate are modulated by molecular context J Biol Chem 269 3957–62 Occurrence Handle8307950 Occurrence Handle1:CAS:528:DyaK2cXhsFOju7Y%3D
A Woods JB McCarthy LT Furcht JR Couchman (1993) ArticleTitleA synthetic peptide from the COOH-terminal heparin-binding domain of fibronectin promotes focal adhesion formation Mol Biol Cell 4 605–13 Occurrence Handle8374170 Occurrence Handle1:CAS:528:DyaK3sXmt1altLY%3D
K Ostergaard DM Salter CB Andersen J Petersen K Bendtzen (1997) ArticleTitleCD44 expression is up-regulated in the deep zone of osteoarthritic cartilage from human femoral heads Histopathology 31 451–9 10.1046/j.1365-2559.1997.2760879.x Occurrence Handle9416486 Occurrence Handle10.1046/j.1365-2559.1997.2760879.x Occurrence Handle1:STN:280:DyaK1c%2FnvVCntA%3D%3D
T Takagi R Okamoto K Suzuki T Hayashi M Sato M Sato et al. (2001) ArticleTitleUp-regulation of CD44 in rheumatoid chondrocytes Scand J Rheumatol 30 110–3 10.1080/03009740151095420 Occurrence Handle11324787 Occurrence Handle10.1080/03009740151095420 Occurrence Handle1:STN:280:DC%2BD3M3kvFCrsQ%3D%3D
G Chow CB Knudson G Homandberg W Knudson (1995) ArticleTitleIncreased expression of CD44 in bovine articular chondrocytes by catabolic cellular mediators J Biol Chem 270 27734–41 10.1074/jbc.270.46.27734 Occurrence Handle7499241 Occurrence Handle10.1074/jbc.270.46.27734 Occurrence Handle1:CAS:528:DyaK2MXpsFShtL8%3D
HJ Hauselmann MB Aydelotte BL Schumacher KE Kuettner SH Gitelis EJ Thonar (1992) ArticleTitleSynthesis and turnover of proteoglycans by human and bovine adult articular chondrocytes cultured in alginate beads Matrix 12 116–29 Occurrence Handle1603034 Occurrence Handle1:CAS:528:DyaK38XisFakurY%3D
JL Rutter U Benbow CI Coon CE Brinckerhoff (1997) ArticleTitleCell-type specific regulation of human interstitial collagense-1 gene expression by interleukin-1β (IL-1β) in human fibroblasts and BC-8701 breast cancer cells J Cell Biochem 66 322–36 10.1002/(SICI)1097-4644(19970901)66:3<322::AID-JCB5>3.0.CO;2-R Occurrence Handle9257189 Occurrence Handle10.1002/(SICI)1097-4644(19970901)66:3<322::AID-JCB5>3.0.CO;2-R Occurrence Handle1:CAS:528:DyaK2sXlt1SitLs%3D
AM Pendas M Balbin E Llano MG Jimenez C Lopez-Otin (1997) ArticleTitleStructural analysis and promoter characterization of human collagenase-3 gene (MMP-13) Genomics 40 222–33 10.1006/geno.1996.4554 Occurrence Handle9119388 Occurrence Handle10.1006/geno.1996.4554 Occurrence Handle1:CAS:528:DyaK2sXhvVOnsrY%3D
M Karin ZG Liu E Zandi (1997) ArticleTitleAP-1 function and regulation Curr Opin Cell Biol 9 240–6 10.1016/S0955-0674(97)80068-3 Occurrence Handle9069263 Occurrence Handle10.1016/S0955-0674(97)80068-3 Occurrence Handle1:CAS:528:DyaK2sXisVWlsL0%3D
R Segar EG Krebs (1995) ArticleTitleThe MAPK signaling cascade FASEB J 9 726–35
TP Garrington GL Johnston (1999) ArticleTitleOrganization and regulation of mitogen-activated protein kinase signaling pathways Curr Opin Cell Biol 11 211–8 10.1016/S0955-0674(99)80028-3 Occurrence Handle10209154 Occurrence Handle10.1016/S0955-0674(99)80028-3 Occurrence Handle1:CAS:528:DyaK1MXisFWlsb8%3D
T Yasuda SM Julovi T Hiramitsu M Yoshida T Nakamura (2004) ArticleTitleRequirement of mitogen-activated protein kinase for collagenase production by the fibronectin fragment in human articular chondrocytes in culture Mod Rheumatol 14 54–60 10.1007/s10165-003-0266-1 Occurrence Handle17028806 Occurrence Handle10.1007/s10165-003-0266-1 Occurrence Handle1:CAS:528:DC%2BD2cXivFKmsr4%3D
F Mainiero A Gismondi A Soriani M Cippitelli G Palmieri J Jacobelli et al. (1998) ArticleTitleIntegrin-mediated ras-extracellular regulated kinase (ERK) signaling regulates interferon gamma production in human natural killer cells J Exp Med 188 1267–75 10.1084/jem.188.7.1267 Occurrence Handle9763606 Occurrence Handle10.1084/jem.188.7.1267 Occurrence Handle1:CAS:528:DyaK1cXmsFalsrw%3D
Q Chen MS Kinch TH Lin K Burridge RL Juliano (1994) ArticleTitleIntegrin-mediated cell adhesion activates mitogen-activated protein kinases J Biol Chem 269 26602–5 Occurrence Handle7929388 Occurrence Handle1:CAS:528:DyaK2cXmt1Ogtrc%3D
MP Vincenti CI Coon CE Brinckerhoff (1998) ArticleTitle1998. Nuclear factor κB/p50 activates an element in the distal matrix metalloproteinase 1 promoter in interleukin-1β-stimulated synovial fibroblasts Arthritis Rheum 41 1987–94 10.1002/1529-0131(199811)41:11<1987::AID-ART14>3.0.CO;2-8 Occurrence Handle9811054 Occurrence Handle10.1002/1529-0131(199811)41:11<1987::AID-ART14>3.0.CO;2-8 Occurrence Handle1:CAS:528:DyaK1cXnsFKgu7Y%3D
JA Mengshol MP Vincenti CI Coon A Barchowsky CE Brinckerhoff (2000) ArticleTitleInterleukin-1 induction of collagenase-3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor κB: differential regulation of collagenase 1 and collagenase 3 Arthritis Rheum 43 801–811 10.1002/1529-0131(200004)43:4<801::AID-ANR10>3.0.CO;2-4 Occurrence Handle10765924 Occurrence Handle10.1002/1529-0131(200004)43:4<801::AID-ANR10>3.0.CO;2-4 Occurrence Handle1:CAS:528:DC%2BD3cXivFOitr0%3D
ASJ Baldwin (1996) ArticleTitleThe NF-κB and IκB proteins: new discoveries and insights Ann Rev Immunol 14 649–83 10.1146/annurev.immunol.14.1.649 Occurrence Handle10.1146/annurev.immunol.14.1.649 Occurrence Handle1:CAS:528:DyaK28XitlCgtbc%3D
C Biswas JM Dayer (1979) ArticleTitleStimulation of collagenase production by collagen in mammalian cell cultures Cell 18 1035–41 10.1016/0092-8674(79)90216-2 Occurrence Handle229968 Occurrence Handle10.1016/0092-8674(79)90216-2 Occurrence Handle1:CAS:528:DyaL3cXls1Wisg%3D%3D
JM Dayer DE Trentham JR David SM Krane (1980) ArticleTitleCollagens stimulate the production of mononuclear cell factor (MCF) and prostaglandins (PGE2) by human monocytes Trans Assoc Am Phys 93 326–35 Occurrence Handle7018066 Occurrence Handle1:CAS:528:DyaL3MXhsFCktbY%3D
JM Dayer DE Trentham SM Krane (1982) ArticleTitleCollagens act as ligands to stimulate human monocytes to produce mononuclear cell factor (MCF) and prostaglandins (PGE2) Collagen Rel Res 2 523–40 Occurrence Handle1:CAS:528:DyaL3sXosVWgsA%3D%3D
KG Jeng M Liu J Lan C Wu DW Wong BM Cheung (1995) ArticleTitleCollagen induces cytokine production by synovial fluid mononuclear cells in rheumatoid arthritis Immunol Lett 45 13–7 10.1016/0165-2478(94)00195-W Occurrence Handle7622181 Occurrence Handle10.1016/0165-2478(94)00195-W Occurrence Handle1:CAS:528:DyaK2MXkvFGqu78%3D
M Goto S Yoshinoya T Miyamoto M Sasano M Okamoto K Nishioka et al. (1988) ArticleTitleStimulation of interleukin-1α and interleukin-1β release from human monocytes by cyanogen bromide peptides of type II collagen Arthritis Rheum 31 1508–14 Occurrence Handle3264163 Occurrence Handle10.1002/art.1780311207 Occurrence Handle1:CAS:528:DyaL1MXntlKlsQ%3D%3D
L Jennings L Wu KB King H Hammerle G Cs-Szabo J Mollenauer (2001) ArticleTitleThe effects of collagen fragments on the extracellular metabolism of bovine and human chondrocytes Connect Tiss Res 42 71–86 Occurrence Handle10.3109/03008200109014250 Occurrence Handle1:CAS:528:DC%2BD38Xlt12htrw%3D
Yasuda T, Mwale F, Burgess J, Poole AR. Type II collagen fragments alter type II and IX collagen turnover in bovine articular chondrocyte culture. Orthopaed Trans 1999;336
W Knudson B Casey Y Nishida W Eger KE Kuettner CB Knudson (2000) ArticleTitleHyaluronan oligosaccharides perturb cartilage matrix homeostasis and induce chondrocytic chondrolysis Arthritis Rheum 43 1165–74 10.1002/1529-0131(200005)43:5<1165::AID-ANR27>3.0.CO;2-H Occurrence Handle10817571 Occurrence Handle10.1002/1529-0131(200005)43:5<1165::AID-ANR27>3.0.CO;2-H Occurrence Handle1:CAS:528:DC%2BD3cXjvVeiu78%3D
S Iacob CB Knudson (2006) ArticleTitleHyaluronan fragments activate nitric oxide synthase and the production of nitric oxide by articular chondrocytes Int J Biochem Cell Biol 38 123–33 10.1016/j.biocel.2005.08.011 Occurrence Handle16181799 Occurrence Handle10.1016/j.biocel.2005.08.011 Occurrence Handle1:CAS:528:DC%2BD2MXhtFOmtL%2FN
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
This article is published under an open access license. Please check the 'Copyright Information' section either on this page or in the PDF for details of this license and what re-use is permitted. If your intended use exceeds what is permitted by the license or if you are unable to locate the licence and re-use information, please contact the Rights and Permissions team.
About this article
Cite this article
Yasuda, T. Cartilage destruction by matrix degradation products. Mod Rheumatol 16, 197–205 (2006). https://doi.org/10.1007/s10165-006-0490-6
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10165-006-0490-6