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Cartilage Proteoglycans

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Abstract

Proteoglycans are key components of the cartilage extracellular matrix and essential for normal tissue function. The core protein and the glycosaminoglycan chains both contribute to function and provide different properties of the individual proteoglycans. This review is focused on the two main families of cartilage proteoglycans.

The first of these is the lectican family, including aggrecan, versican, and the cartilage link protein. The aggregating proteoglycan network formed by aggrecan, link protein, and hyaluronan provides biomechanical properties that give the tissue its ability to withstand and distribute load.

The second group discussed is the small leucine-rich repeat proteoglycan family, which includes decorin, biglycan, asporin, fibromodulin, lumican, keratocan, osteoadherin, proline-/arginine-rich end leucine-rich repeat protein, epiphycan, mimecan, opticin, chondroadherin, and chondroadherin-like. These proteoglycans bind collagens and are important regulators of cartilage extracellular matrix assembly. In addition, some of these proteoglycans bind and regulate growth factors and their receptors and regulate innate immunity through interactions with Toll-like receptors or the complement system.

This review will give an overview of the structure and function of the different aggregating proteoglycans and small leucine-rich repeat proteoglycans in normal cartilage extracellular matrix.

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References

  • Ameye L, Aria D, Jepsen K, Oldberg Å, Xu T, Young MF (2002) Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis. FASEB J 16(7):673–680. doi:10.1096/fj.01-0848com

    Article  CAS  PubMed  Google Scholar 

  • Antonsson P, Heinegård D, Oldberg Å (1991) Posttranslational modifications of fibromodulin. J Biol Chem 266(25):16859–16861

    CAS  PubMed  Google Scholar 

  • Aspberg A (2012) The different roles of aggrecan interaction domains. J Histochem Cytochem 60(12):987–996. doi:10.1369/0022155412464376

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Awata T, Yamada S, Tsushima K, Sakashita H, Yamaba S, Kajikawa T, Yamashita M, Takedachi M, Yanagita M, Kitamura M, Murakami S (2015) PLAP-1/asporin positively regulates FGF-2 activity. J Dent Res 94(10):1417–1424. doi:10.1177/0022034515598507

    Article  CAS  PubMed  Google Scholar 

  • Barry FP, Rosenberg LC, Gaw JU, Koob TJ, Neame PJ (1995) N- and O-linked keratan sulfate on the hyaluronan binding region of aggrecan from mature and immature bovine cartilage. J Biol Chem 270(35):20516–20524 [published erratum appears in J Biol Chem 1995 Dec 29;270(52):31414]

    Article  CAS  PubMed  Google Scholar 

  • Batista MA, Nia HT, Önnerfjord P, Cox KA, Ortiz C, Grodzinsky AJ, Heinegård D, Han L (2014) Nanomechanical phenotype of chondroadherin-null murine articular cartilage. Matrix Biol 38:84–90. doi:10.1016/j.matbio.2014.05.008

    Article  CAS  PubMed  Google Scholar 

  • Bengtsson E, Aspberg A, Heinegård D, Sommarin Y, Spillmann D (2000) The amino-terminal part of PRELP binds to heparin and heparan sulfate. J Biol Chem 275:40695–40702

    Article  CAS  PubMed  Google Scholar 

  • Bengtsson E, Mörgelin M, Sasaki T, Timpl R, Heinegård D, Aspberg A (2002) The leucine-rich repeat protein PRELP binds perlecan and collagens and may function as a basement membrane anchor. J Biol Chem 277(17):15061–15068

    Article  CAS  PubMed  Google Scholar 

  • Bengtsson E, Neame PJ, Heinegård D, Sommarin Y (1995) The primary structure of a basic leucine-rich repeat protein, PRELP, found in connective tissues. J Biol Chem 270(43):25639–25644

    Article  CAS  PubMed  Google Scholar 

  • Berendsen AD, Pinnow EL, Maeda A, Brown AC, McCartney-Francis N, Kram V, Owens RT, Robey PG, Holmbeck K, de Castro LF, Kilts TM, Young MF (2014) Biglycan modulates angiogenesis and bone formation during fracture healing. Matrix Biol 35:223–231. doi:10.1016/j.matbio.2013.12.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bode-Lesniewska B, Dours-Zimmermann MT, Odermatt BF, Briner J, Heitz PU, Zimmermann DR (1996) Distribution of the large aggregating proteoglycan versican in adult human tissues. J Histochem Cytochem 44(4):303–312

    Article  CAS  PubMed  Google Scholar 

  • Camper L, Heinegård D, Lundgren-Åkerlund E (1997) Integrin alpha2beta1 is a receptor for the cartilage matrix protein chondroadherin. J Cell Biol 138(5):1159–1167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Capulli M, Olstad OK, Önnerfjord P, Tillgren V, Muraca M, Gautvik KM, Heinegård D, Rucci N, Teti A (2014) The C-terminal domain of chondroadherin: a new regulator of osteoclast motility counteracting bone loss. J Bone Miner Res 29(8):1833–1846. doi:10.1002/jbmr.2206

    Article  CAS  PubMed  Google Scholar 

  • Chakravarti S, Magnuson T, Lass JH, Jepsen KJ, LaMantia C, Carroll H (1998) Lumican regulates collagen fibril assembly: skin fragility and corneal opacity in the absence of lumican. J Cell Biol 141(5):1277–1286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choocheep K, Hatano S, Takagi H, Watanabe H, Kimata K, Kongtawelert P, Watanabe H (2010) Versican facilitates chondrocyte differentiation and regulates joint morphogenesis. J Biol Chem 285(27):21114–21125. doi:10.1074/jbc.M109.096479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Corpuz LM, Funderburgh JL, Funderburgh ML, Bottomley GS, Prakash S, Conrad GW (1996) Molecular cloning and tissue distribution of keratocan. Bovine corneal keratan sulfate proteoglycan 37A. J Biol Chem 271(16):9759–9763

    Google Scholar 

  • Corsi A, Xu T, Chen XD, Boyde A, Liang J, Mankani M, Sommer B, Iozzo RV, Eichstetter I, Robey PG, Bianco P, Young MF (2002) Phenotypic effects of biglycan deficiency are linked to collagen fibril abnormalities, are synergized by decorin deficiency, and mimic Ehlers-Danlos-like changes in bone and other connective tissues. J Bone Miner Res 17(7):1180–1189. doi:10.1359/jbmr.2002.17.7.1180

    Article  CAS  PubMed  Google Scholar 

  • Cs-Szabo G, Melching LI, Roughley PJ, Glant TT (1997) Changes in messenger RNA and protein levels of proteoglycans and link protein in human osteoarthritic cartilage samples. Arthritis Rheum 40(6):1037–1045. doi:10.1002/1529-0131(199706)40:6<1037::AID-ART6>3.0.CO;2-A

    Article  CAS  PubMed  Google Scholar 

  • Danielson KG, Baribault H, Holmes DF, Graham H, Kadler KE, Iozzo RV (1997) Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J Cell Biol 136(3):729–743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deak F, Kiss I, Sparks KJ, Argraves WS, Hampikian G, Goetinck PF (1986) Complete amino acid sequence of chicken cartilage link protein deduced from cDNA clones. Proc Natl Acad Sci U S A 83(11):3766–3770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deere M, Johnson J, Garza S, Harrison WR, Yoon SJ, Elder FFB, Kucherlapati R, Hook M, Hecht JT (1996) Characterization of human DSPG3, a small dermatan sulfate proteoglycan. Genomics 38(3):399–404

    Article  CAS  PubMed  Google Scholar 

  • Doege K, Hassell JR, Caterson B, Yamada Y (1986) Link protein cDNA sequence reveals a tandemly repeated protein structure. Proc Natl Acad Sci U S A 83(11):3761–3765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doege K, Sasaki M, Horigan E, Hassell JR, Yamada Y (1987) Complete primary structure of the rat cartilage proteoglycan core protein deduced from cDNA clones. J Biol Chem 262(36):17757–17767 [published erratum appears in J Biol Chem 1988 Jul 15;263(20):10040]

    CAS  PubMed  Google Scholar 

  • Dours-Zimmermann MT, Zimmermann DR (1994) A novel glycosaminoglycan attachment domain identified in two alternative splice variants of human versican. J Biol Chem 269(52):32992–32998

    CAS  PubMed  Google Scholar 

  • Grover J, Chen XN, Korenberg JR, Roughley PJ (1995) The human lumican gene. Organization, chromosomal location, and expression in articular cartilage. J Biol chem 270(37):21942–21949

    Google Scholar 

  • Fisher LW, Termine JD, Dejter SW Jr, Whitson SW, Yanagishita M, Kimura JH, Hascall VC, Kleinman HK, Hassell JR, Nilsson B (1983) Proteoglycans of developing bone. J Biol Chem 258(10):6588–6594

    CAS  PubMed  Google Scholar 

  • Fisher LW, Termine JD, Young MF (1989) Deduced protein sequence of bone small proteoglycan I (biglycan) shows homology with proteoglycan II (decorin) and several nonconnective tissue proteins in a variety of species. J Biol Chem 264(8):4571–4576

    CAS  PubMed  Google Scholar 

  • Friedman JS, Ducharme R, Raymond V, Walter MA (2000) Isolation of a novel iris-specific and leucine-rich repeat protein (oculoglycan) using differential selection. Invest Ophthalmol Vis Sci 41(8):2059–2066

    CAS  PubMed  Google Scholar 

  • Funderburgh JL, Corpuz LM, Roth MR, Funderburgh ML, Tasheva ES, Conrad GW (1997) Mimecan, the 25-kDa corneal keratan sulfate proteoglycan, is a product of the gene producing osteoglycin. J Biol Chem 272(44):28089–28095

    Article  CAS  PubMed  Google Scholar 

  • Geng Y, McQuillan D, Roughley PJ (2006) SLRP interaction can protect collagen fibrils from cleavage by collagenases. Matrix Biol 25(8):484–491. doi:10.1016/j.matbio.2006.08.259

    Article  CAS  PubMed  Google Scholar 

  • Gill MR, Oldberg Å, Reinholt FP (2002) Fibromodulin-null murine knee joints display increased incidences of osteoarthritis and alterations in tissue biochemistry. Osteoarthritis Cartilage 10(10):751–757

    Article  CAS  PubMed  Google Scholar 

  • Groeneveld TW, Oroszlan M, Owens RT, Faber-Krol MC, Bakker AC, Arlaud GJ, McQuillan DJ, Kishore U, Daha MR, Roos A (2005) Interactions of the extracellular matrix proteoglycans decorin and biglycan with C1q and collectins. J Immunol 175(7):4715–4723

    Article  CAS  PubMed  Google Scholar 

  • Grover J, Roughley PJ (1998) Characterization of the human proline/arginine-rich end leucine-rich repeat protein (PRELP) gene promoter and identification of a repressor element. Biochem J 336(Pt 1):77–82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grover J, Roughley PJ (2001) Characterization and expression of murine PRELP. Matrix Biol 20(8):555–564

    Article  CAS  PubMed  Google Scholar 

  • Haglund L, Tillgren V, Addis L, Wenglén C, Recklies A, Heinegård D (2011) Identification and characterization of the integrin alpha2beta1 binding motif in chondroadherin mediating cell attachment. J Biol Chem 286(5):3925–3934. doi:10.1074/jbc.M110.161141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haglund L, Tillgren V, Önnerfjord P, Heinegård D (2013) The C-terminal peptide of chondroadherin modulates cellular activity by selectively binding to heparan sulfate chains. J Biol Chem 288(2):995–1008. doi:10.1074/jbc.M112.430512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han L, Grodzinsky AJ, Ortiz C (2011) Nanomechanics of the cartilage extracellular matrix. Annu Rev Mater Res 41:133–168. doi:10.1146/annurev-matsci-062910-100431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Happonen KE, Sjöberg AP, Mörgelin M, Heinegård D, Blom AM (2009) Complement inhibitor C4b-binding protein interacts directly with small glycoproteins of the extracellular matrix. J Immunol 182(3):1518–1525, 182/3/1518 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Hardingham TE (1979) The role of link-protein in the structure of cartilage proteoglycan aggregates. Biochem J 177(1):237–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heathfield TF, Önnerfjord P, Dahlberg L, Heinegård D (2004) Cleavage of fibromodulin in cartilage explants involves removal of the N-terminal tyrosine sulfate-rich region by proteolysis at a site that is sensitive to matrix metalloproteinase-13. J Biol Chem 279(8):6286–6295. doi:10.1074/jbc.M307765200, M307765200 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Hedbom E, Heinegård D (1989) Interaction of a 59-kDa connective tissue matrix protein with collagen I and collagen II. J Biol Chem 264(12):6898–6905

    CAS  PubMed  Google Scholar 

  • Hedlund H, Hedbom E, Heinegård D, Mengarelli-Widholm S, Reinholt FP, Svensson O (1999) Association of the aggrecan keratan sulfate-rich region with collagen in bovine articular cartilage. J Biol Chem 274(9):5777–5781

    Article  CAS  PubMed  Google Scholar 

  • Hedlund H, Mengarelli-Widholm S, Heinegård D, Reinholt FP, Svensson O (1994) Fibromodulin distribution and association with collagen. Matrix Biol 14(3):227–232

    Article  CAS  PubMed  Google Scholar 

  • Heinegård D (2009) Proteoglycans and more--from molecules to biology. Int J Exp Pathol 90(6):575–586. IEP695 [pii]. doi:10.1111/j.1365-2613.2009.00695.x

    Google Scholar 

  • Heinegård D, Hascall VC (1974) Aggregation of cartilage proteoglycans. 3. Characteristics of the proteins isolated from trypsin digests of aggregates. J Biol Chem 249(13):4250–4256

    PubMed  Google Scholar 

  • Heinegård D, Larsson T, Sommarin Y, Franzén A, Paulsson M, Hedbom E (1986) Two novel matrix proteins isolated from articular cartilage show wide distributions among connective tissues. J Biol Chem 261(29):13866–13872

    PubMed  Google Scholar 

  • Heinegård D, Saxne T (2011) The role of the cartilage matrix in osteoarthritis. Nat Rev Rheumatol 7(1):50–56. nrrheum.2010.198 [pii]. doi:10.1038/nrrheum.2010.198

    Google Scholar 

  • Henry SP, Takanosu M, Boyd TC, Mayne PM, Eberspaecher H, Zhou W, de Crombrugghe B, Hook M, Mayne R (2001) Expression pattern and gene characterization of asporin. A newly discovered member of the leucine-rich repeat protein family. J Biol Chem 276(15):12212–12221. doi:10.1074/jbc.M011290200

    Article  CAS  PubMed  Google Scholar 

  • Hessle L, Stordalen GA, Wenglen C, Petzold C, Tanner EK, Brorson SH, Baekkevold ES, Önnerfjord P, Reinholt FP, Heinegård D (2013) The skeletal phenotype of chondroadherin deficient mice. PLoS One 8(6), e63080. doi:10.1371/journal.pone.0063080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hindson VJ, Gallagher JT, Halfter W, Bishop PN (2005) Opticin binds to heparan and chondroitin sulfate proteoglycans. Invest Ophthalmol Vis Sci 46(12):4417–4423. doi:10.1167/iovs.05-0883

    Article  PubMed  Google Scholar 

  • Hobby P, Wyatt MK, Gan W, Bernstein S, Tomarev S, Slingsby C, Wistow G (2000) Cloning, modeling, and chromosomal localization for a small leucine- rich repeat proteoglycan (SLRP) family member expressed in human eye. Mol Vis 6:72–78

    CAS  PubMed  Google Scholar 

  • Iozzo RV, Schaefer L (2015) Proteoglycan form and function: a comprehensive nomenclature of proteoglycans. Matrix Biol 42:11–55. doi:10.1016/j.matbio.2015.02.003

    Article  CAS  PubMed  Google Scholar 

  • Islam M, Gor J, Perkins SJ, Ishikawa Y, Bachinger HP, Hohenester E (2013) The concave face of decorin mediates reversible dimerization and collagen binding. J Biol Chem 288(49):35526–35533. doi:10.1074/jbc.M113.504530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson HJ, Rosenberg L, Choi HU, Garza S, Hook M, Neame PJ (1997) Characterization of epiphycan, a small proteoglycan with a leucine-rich repeat core protein. J Biol Chem 272(30):18709–18717

    Article  CAS  PubMed  Google Scholar 

  • Kalamajski S, Aspberg A, Lindblom K, Heinegård D, Oldberg Å (2009) Asporin competes with decorin for collagen binding, binds calcium and promotes osteoblast collagen mineralization. Biochem J 423(1):53–59. BJ20090542 [pii]. doi:10.1042/BJ20090542

    Google Scholar 

  • Kalamajski S, Aspberg A, Oldberg Å (2007) The decorin sequence SYIRIADTNIT binds collagen type I. J Biol Chem 282(22):16062–16067. M700073200 [pii]. doi:10.1074/jbc.M700073200

    Google Scholar 

  • Kalamajski S, Liu C, Tillgren V, Rubin K, Oldberg Å, Rai J, Weis M, Eyre DR (2014) Increased C-telopeptide cross-linking of tendon type I collagen in fibromodulin-deficient mice. J Biol Chem 289(27):18873–18879. doi:10.1074/jbc.M114.572941

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalamajski S, Oldberg Å (2009) Homologous sequence in lumican and fibromodulin leucine-rich repeat 5-7 competes for collagen binding. J Biol Chem 284(1):534–539. M805721200 [pii]. doi:10.1074/jbc.M805721200

    Google Scholar 

  • Kalamajski S, Oldberg Å (2010) The role of small leucine-rich proteoglycans in collagen fibrillogenesis. Matrix Biol 29(4):248–253. S0945-053X(10)00005-3 [pii]. doi:10.1016/j.matbio.2010.01.001

    Google Scholar 

  • Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y, Luo JL, Karin M (2009) Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 457(7225):102–106. doi:10.1038/nature07623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kizawa H, Kou I, Iida A, Sudo A, Miyamoto Y, Fukuda A, Mabuchi A, Kotani A, Kawakami A, Yamamoto S, Uchida A, Nakamura K, Notoya K, Nakamura Y, Ikegawa S (2005) An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis. Nat Genet 37(2):138–144

    Article  CAS  PubMed  Google Scholar 

  • Kou I, Nakajima M, Ikegawa S (2010) Binding characteristics of the osteoarthritis-associated protein asporin. J Bone Miner Metab 28(4):395–402. doi:10.1007/s00774-009-0145-8

    Article  CAS  PubMed  Google Scholar 

  • Krumdieck R, Hook M, Rosenberg LC, Volanakis JE (1992) The proteoglycan decorin binds C1q and inhibits the activity of the C1 complex. J Immunol 149(11):3695–3701

    CAS  PubMed  Google Scholar 

  • Krusius T, Ruoslahti E (1986) Primary structure of an extracellular matrix proteoglycan core protein deduced from cloned cDNA. Proc Natl Acad Sci U S A 83(20):7683–7687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kurita K, Shinomura T, Ujita M, Zako M, Kida D, Iwata H, Kimata K (1996) Occurrence of PG-Lb, a leucine-rich small chondroitin/dermatan sulphate proteoglycan in mammalian epiphyseal cartilage: molecular cloning and sequence analysis of the mouse cDNA. Biochem J 318(Pt 3):909–914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • LeBaron RG, Zimmermann DR, Ruoslahti E (1992) Hyaluronate binding properties of versican. J Biol Chem 267(14):10003–10010

    CAS  PubMed  Google Scholar 

  • Lees S, Golub SB, Last K, Zeng W, Jackson DC, Sutton P, Fosang AJ (2015) Bioactivity in an aggrecan 32-mer fragment is mediated via toll-like receptor 2. Arthritis Rheumatol (Hoboken, NJ) 67(5):1240–1249. doi:10.1002/art.39063

    Article  CAS  Google Scholar 

  • Liu CY, Birk DE, Hassell JR, Kane B, Kao WW (2003) Keratocan-deficient mice display alterations in corneal structure. J Biol Chem 278(24):21672–21677. doi:10.1074/jbc.M301169200

    Article  CAS  PubMed  Google Scholar 

  • Liu H, McKenna LA, Dean MF (2000) An N-terminal peptide from link protein can stimulate biosynthesis of collagen by human articular cartilage. Arch Biochem Biophys 378(1):116–122. doi:10.1006/abbi.2000.1758

    Article  CAS  PubMed  Google Scholar 

  • Lorenzo P, Aspberg A, Önnerfjord P, Bayliss MT, Neame PJ, Heinegård D (2001) Identification and characterization of asporin. a novel member of the leucine-rich repeat protein family closely related to decorin and biglycan. J Biol Chem 276(15):12201–12211

    Article  CAS  PubMed  Google Scholar 

  • Luehders K, Sasai N, Davaapil H, Kurosawa-Yoshida M, Hiura H, Brah T, Ohnuma S (2015) The small leucine-rich repeat secreted protein Asporin induces eyes in Xenopus embryos through the IGF signalling pathway. Development 142(19):3351–3361. doi:10.1242/dev.124438

    Article  CAS  PubMed  Google Scholar 

  • Malmsten M, Davoudi M, Schmidtchen A (2006) Bacterial killing by heparin-binding peptides from PRELP and thrombospondin. Matrix Biol 25(5):294–300. doi:10.1016/j.matbio.2006.04.003

    Article  CAS  PubMed  Google Scholar 

  • Malmsten M, Kasetty G, Pasupuleti M, Alenfall J, Schmidtchen A (2011) Highly selective end-tagged antimicrobial peptides derived from PRELP. PLoS One 6(1), e16400. doi:10.1371/journal.pone.0016400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Månsson B, Wenglen C, Mörgelin M, Saxne T, Heinegård D (2001) Association of chondroadherin with collagen type II. J Biol Chem 276(35):32883–32888. doi:10.1074/jbc.M101680200

    Article  PubMed  Google Scholar 

  • Maroudas A, Bayliss MT, Uchitel-Kaushansky N, Schneiderman R, Gilav E (1998) Aggrecan turnover in human articular cartilage: use of aspartic acid racemization as a marker of molecular age. Arch Biochem Biophys 350(1):61–71. doi:10.1006/abbi.1997.0492

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto K, Kamiya N, Suwan K, Atsumi F, Shimizu K, Shinomura T, Yamada Y, Kimata K, Watanabe H (2006) Identification and characterization of versican/PG-M aggregates in cartilage. J Biol Chem 281(26):18257–18263

    Article  CAS  PubMed  Google Scholar 

  • McCulloch DR, Nelson CM, Dixon LJ, Silver DL, Wylie JD, Lindner V, Sasaki T, Cooley MA, Argraves WS, Apte SS (2009) ADAMTS metalloproteases generate active versican fragments that regulate interdigital web regression. Dev Cell 17(5):687–698. doi:10.1016/j.devcel.2009.09.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McKenna LA, Liu H, Sansom PA, Dean MF (1998) An N-terminal peptide from link protein stimulates proteoglycan biosynthesis in human articular cartilage in vitro. Arthritis Rheum 41(1):157–162. doi:10.1002/1529-0131(199801)41:1<157::aid-art19>3.0.co;2-j

    Article  CAS  PubMed  Google Scholar 

  • Melin Fürst C, Mörgelin M, Vadstrup K, Heinegård D, Aspberg A, Blom AM (2013) The C-type lectin of the aggrecan G3 domain activates complement. PLoS One 8(4), e61407. doi:10.1371/journal.pone.0061407

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mikami T, Kitagawa H (2013) Biosynthesis and function of chondroitin sulfate. Biochim Biophys Acta 1830(10):4719–4733. doi:10.1016/j.bbagen.2013.06.006

    Article  CAS  PubMed  Google Scholar 

  • Monfort J, Tardif G, Roughley P, Reboul P, Boileau C, Bishop PN, Pelletier JP, Martel-Pelletier J (2008) Identification of opticin, a member of the small leucine-rich repeat proteoglycan family, in human articular tissues: a novel target for MMP-13 in osteoarthritis. Osteoarthritis Cartilage 16(7):749–755. doi:10.1016/j.joca.2007.11.007

    Article  CAS  PubMed  Google Scholar 

  • Müller C, Khabut A, Dudhia J, Reinholt FP, Aspberg A, Heinegård D, Önnerfjord P (2014) Quantitative proteomics at different depths in human articular cartilage reveals unique patterns of protein distribution. Matrix Biol 40:34–45. doi:10.1016/j.matbio.2014.08.013

    Article  PubMed  CAS  Google Scholar 

  • Nakajima M, Kizawa H, Saitoh M, Kou I, Miyazono K, Ikegawa S (2007) Mechanisms for asporin function and regulation in articular cartilage. J Biol Chem 282(44):32185–32192. doi:10.1074/jbc.M700522200

    Article  CAS  PubMed  Google Scholar 

  • Nakamura T, Shi D, Tzetis M, Rodriguez-Lopez J, Miyamoto Y, Tsezou A, Gonzalez A, Jiang Q, Kamatani N, Loughlin J, Ikegawa S (2007) Meta-analysis of association between the ASPN D-repeat and osteoarthritis. Hum Mol Genet 16(14):1676–1681. doi:10.1093/hmg/ddm115

    Article  CAS  PubMed  Google Scholar 

  • Nandadasa S, Foulcer S, Apte SS (2014) The multiple, complex roles of versican and its proteolytic turnover by ADAMTS proteases during embryogenesis. Matrix Biol 35:34–41. doi:10.1016/j.matbio.2014.01.005

    Article  CAS  PubMed  Google Scholar 

  • Nastase MV, Young MF, Schaefer L (2012) Biglycan: a multivalent proteoglycan providing structure and signals. J Histochem Cytochem 60(12):963–975. doi:10.1369/0022155412456380

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Neame PJ, Christner JE, Baker JR (1986) The primary structure of link protein from rat chondrosarcoma proteoglycan aggregate. J Biol Chem 261(8):3519–3535

    CAS  PubMed  Google Scholar 

  • Neame PJ, Sommarin Y, Boynton RE, Heinegård D (1994) The structure of a 38-kDa leucine-rich protein (chondroadherin) isolated from bovine cartilage. J Biol Chem 269(34):21547–21554

    CAS  PubMed  Google Scholar 

  • Nilsson O, Guo MH, Dunbar N, Popovic J, Flynn D, Jacobsen C, Lui JC, Hirschhorn JN, Baron J, Dauber A (2014) Short stature, accelerated bone maturation, and early growth cessation due to heterozygous aggrecan mutations. J Clin Endocrinol Metab 99(8):E1510–E1518. doi:10.1210/jc.2014-1332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishida Y, Shinomura T, Iwata H, Miura T, Kimata K (1994) Abnormal occurrence of a large chondroitin sulfate proteoglycan, PG-M/versican in osteoarthritic cartilage. Osteoarthritis Cartilage 2:43–49

    Article  CAS  PubMed  Google Scholar 

  • Noborn F, Gomez Toledo A, Sihlbom C, Lengqvist J, Fries E, Kjellen L, Nilsson J, Larson G (2015) Identification of chondroitin sulfate linkage region glycopeptides reveals prohormones as a novel class of proteoglycans. Mol Cell Proteomics: MCP 14(1):41–49. doi:10.1074/mcp.M114.043703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nuka S, Zhou W, Henry SP, Gendron CM, Schultz JB, Shinomura T, Johnson J, Wang Y, Keene DR, Ramirez-Solis R, Behringer RR, Young MF, Hook M (2010) Phenotypic characterization of epiphycan-deficient and epiphycan/biglycan double-deficient mice. Osteoarthritis Cartilage 18(1):88–96. doi:10.1016/j.joca.2009.11.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oldberg Å, Antonsson P, Lindblom K, Heinegård D (1989) A collagen-binding 59-kd protein (fibromodulin) is structurally related to the small interstitial proteoglycans PG-S1 and PG-S2 (decorin). EMBO J 8(9):2601–2604

    CAS  PubMed  PubMed Central  Google Scholar 

  • Önnerfjord P, Heathfield TF, Heinegård D (2004) Identification of tyrosine sulfation in extracellular leucine-rich repeat proteins using mass spectrometry. J Biol Chem 279(1):26–33. doi:10.1074/jbc.M308689200

    Article  PubMed  CAS  Google Scholar 

  • Önnerfjord P, Khabut A, Reinholt FP, Svensson O, Heinegård D (2012) Quantitative proteomic analysis of eight cartilaginous tissues reveals characteristic differences as well as similarities between subgroups. J Biol Chem 287(23):18913–18924. doi:10.1074/jbc.M111.298968

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Orgel JP, Eid A, Antipova O, Bella J, Scott JE (2009) Decorin core protein (decoron) shape complements collagen fibril surface structure and mediates its binding. PLoS One 4(9), e7028. doi:10.1371/journal.pone.0007028

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Orlowsky EW, Kraus VB (2015) The role of innate immunity in osteoarthritis: when our first line of defense goes on the offensive. J Rheumatol 42(3):363–371. doi:10.3899/jrheum.140382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park H, Huxley-Jones J, Boot-Handford RP, Bishop PN, Attwood TK, Bella J (2008) LRRCE: a leucine-rich repeat cysteine capping motif unique to the chordate lineage. BMC Genomics 9:599. doi:10.1186/1471-2164-9-599

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Plaas AH, Neame PJ, Nivens CM, Reiss L (1990) Identification of the keratan sulfate attachment sites on bovine fibromodulin. J Biol Chem 265(33):20634–20640

    CAS  PubMed  Google Scholar 

  • Reardon AJ, Le Goff M, Briggs MD, McLeod D, Sheehan JK, Thornton DJ, Bishop PN (2000) Identification in vitreous and molecular cloning of opticin, a novel member of the family of leucine-rich repeat proteins of the extracellular matrix. J Biol Chem 275(3):2123–2129

    Article  CAS  PubMed  Google Scholar 

  • Rees SG, Waggett AD, Kerr BC, Probert J, Gealy EC, Dent CM, Caterson B, Hughes CE (2009) Immunolocalisation and expression of keratocan in tendon. Osteoarthritis Cartilage 17(2):276–279. doi: 10.1016/j.joca.2008.07.007

    Google Scholar 

  • Rosenberg LC, Choi HU, Tang LH, Johnson TL, Pal S, Webber C, Reiner A, Poole AR (1985) Isolation of dermatan sulfate proteoglycans from mature bovine articular cartilages. J Biol Chem 260(10):6304–6313

    CAS  PubMed  Google Scholar 

  • Roughley PJ, White RJ, Cs-Szabo G, Mort JS (1996) Changes with age in the structure of fibromodulin in human articular cartilage. Osteoarthritis Cartilage 4(3):153–161

    Google Scholar 

  • Rucci N, Capulli M, Olstad OK, Önnerfjord P, Tillgren V, Gautvik KM, Heinegård D, Teti A (2015) The alpha2beta1 binding domain of chondroadherin inhibits breast cancer-induced bone metastases and impairs primary tumour growth: a preclinical study. Cancer Lett 358(1):67–75. doi:10.1016/j.canlet.2014.12.032

    Article  CAS  PubMed  Google Scholar 

  • Rucci N, Capulli M, Ventura L, Angelucci A, Peruzzi B, Tillgren V, Muraca M, Heinegård D, Teti A (2013) Proline/arginine-rich end leucine-rich repeat protein N-terminus is a novel osteoclast antagonist that counteracts bone loss. J Bone Miner Res 28(9):1912–1924. doi:10.1002/jbmr.1951

    Article  CAS  PubMed  Google Scholar 

  • Rucci N, Rufo A, Alamanou M, Capulli M, Del Fattore A, Åhrman E, Capece D, Iansante V, Zazzeroni F, Alesse E, Heinegård D, Teti A (2009) The glycosaminoglycan-binding domain of PRELP acts as a cell type-specific NF-kappaB inhibitor that impairs osteoclastogenesis. J Cell Biol 187(5):69–683. jcb.200906014 [pii]. doi:10.1083/jcb.200906014

    Google Scholar 

  • Ruoslahti E (1988) Structure and biology of proteoglycans. Annu Rev Cell Biol 4:229–255. doi:10.1146/annurev.cb.04.110188.001305

    Article  CAS  PubMed  Google Scholar 

  • Ruoslahti E (1996) Brain extracellular matrix. Glycobiology 6(5):489–492

    Article  CAS  PubMed  Google Scholar 

  • Schaefer L, Babelova A, Kiss E, Hausser HJ, Baliova M, Krzyzankova M, Marsche G, Young MF, Mihalik D, Gotte M, Malle E, Schaefer RM, Grone HJ (2005) The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. J Clin Invest 115(8):2223–2233. doi:10.1172/JCI23755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scott IC, Imamura Y, Pappano WN, Troedel JM, Recklies AD, Roughley PJ, Greenspan DS (2000) Bone morphogenetic protein-1 processes probiglycan. J Biol Chem 275(39):30504–30511

    Article  CAS  PubMed  Google Scholar 

  • Scott JE, Orford CR (1981) Dermatan sulphate-rich proteoglycan associates with rat tail-tendon collagen at the d band in the gap region. Biochem J 197(1):213–216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scott PG, Dodd CM, Bergmann EM, Sheehan JK, Bishop PN (2006) Crystal structure of the biglycan dimer and evidence that dimerization is essential for folding and stability of class I small leucine-rich repeat proteoglycans. J Biol Chem 281(19):13324–13332

    Article  CAS  PubMed  Google Scholar 

  • Scott PG, Grossmann JG, Dodd CM, Sheehan JK, Bishop PN (2003) Light and X-ray scattering show decorin to be a dimer in solution. J Biol Chem 278(20):18353–18359

    Article  CAS  PubMed  Google Scholar 

  • Scott PG, McEwan PA, Dodd CM, Bergmann EM, Bishop PN, Bella J (2004) Crystal structure of the dimeric protein core of decorin, the archetypal small leucine-rich repeat proteoglycan. Proc Natl Acad Sci U S A 101(44):15633–15638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sjöberg A, Önnerfjord P, Mörgelin M, Heinegård D, Blom AM (2005) The extracellular matrix and inflammation: fibromodulin activates the classical pathway of complement by directly binding C1q. J Biol Chem 280(37):32301–32308. M504828200 [pii]. doi:10.1074/jbc.M504828200

    Google Scholar 

  • Sjöberg AP, Manderson GA, Mörgelin M, Day AJ, Heinegård D, Blom AM (2009) Short leucine-rich glycoproteins of the extracellular matrix display diverse patterns of complement interaction and activation. Mol Immunol 46(5):830–839. S0161-5890(08)00661-5 [pii]. doi:10.1016/j.molimm.2008.09.018

    Google Scholar 

  • Sjöberg AP, Trouw LA, Clark SJ, Sjölander J, Heinegård D, Sim RB, Day AJ, Blom AM (2007) The factor H variant associated with age-related macular degeneration (His-384) and the non-disease-associated form bind differentially to C-reactive protein, fibromodulin, DNA, and necrotic cells. J Biol Chem 282(15):10894–10900. M610256200 [pii]. doi:10.1074/jbc.M610256200

    Google Scholar 

  • Sommarin Y, Larsson T, Heinegård D (1989) Chondrocyte-matrix interactions. Attachment to proteins isolated from cartilage. Exp Cell Res 184(1):181–192

    Article  CAS  PubMed  Google Scholar 

  • Sommarin Y, Wendel M, Shen Z, Hellman U, Heinegård D (1998) Osteoadherin, a cell-binding keratan sulfate proteoglycan in bone, belongs to the family of leucine-rich repeat proteins of the extracellular matrix. J Biol Chem 273(27):16723–16729

    Article  CAS  PubMed  Google Scholar 

  • Song GG, Kim JH, Lee YH (2014) A meta-analysis of the relationship between aspartic acid (D)-repeat polymorphisms in asporin and osteoarthritis susceptibility. Rheumatol Int 34(6):785–792. doi:10.1007/s00296-013-2916-8

    Article  CAS  PubMed  Google Scholar 

  • Song YQ, Cheung KM, Ho DW, Poon SC, Chiba K, Kawaguchi Y, Hirose Y, Alini M, Grad S, Yee AF, Leong JC, Luk KD, Yip SP, Karppinen J, Cheah KS, Sham P, Ikegawa S, Chan D (2008) Association of the asporin D14 allele with lumbar-disc degeneration in Asians. Am J Hum Genet 82(3):744–747. doi:10.1016/j.ajhg.2007.12.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spicer AP, Joo A, Bowling RA Jr (2003) A hyaluronan binding link protein gene family whose members are physically linked adjacent to chondroitin sulfate proteoglycan core protein genes: the missing links. J Biol Chem 278(23):21083–21091. doi:10.1074/jbc.M213100200, M213100200 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Lindblom K, Önnerfjord P, Jonsson BA, Tegner Y, Sasaki T, Struglics A, Lohmander S, Dahl N, Heinegård D, Aspberg A (2010) A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans. Am J Hum Genet 86(2):126–137. S0002-9297(10)00012-1 [pii]. doi:10.1016/j.ajhg.2009.12.018

    Google Scholar 

  • Sugars RV, Olsson ML, Marchner S, Hultenby K, Wendel M (2013) The glycosylation profile of osteoadherin alters during endochondral bone formation. Bone 53(2):459–467. doi:10.1016/j.bone.2013.01.022

    Article  CAS  PubMed  Google Scholar 

  • Svensson L, Aszódi A, Reinholt FP, Fässler R, Heinegård D, Oldberg Å (1999) Fibromodulin-null mice have abnormal collagen fibrils, tissue organization, and altered lumican deposition in tendon. J Biol Chem 274(14):9636–9647

    Article  CAS  PubMed  Google Scholar 

  • Svensson L, Heinegård D, Oldberg Å (1995) Decorin-binding sites for collagen type I are mainly located in leucine- rich repeats 4-5. J Biol Chem 270(35):20712–20716

    Article  CAS  PubMed  Google Scholar 

  • Svensson L, Närlid I, Oldberg Å (2000) Fibromodulin and lumican bind to the same region on collagen type I fibrils. FEBS Lett 470(2):178–182

    Article  CAS  PubMed  Google Scholar 

  • Tasheva ES, Koester A, Paulsen AQ, Garrett AS, Boyle DL, Davidson HJ, Song M, Fox N, Conrad GW (2002) Mimecan/osteoglycin-deficient mice have collagen fibril abnormalities. Mol Vis 8:407–415

    CAS  PubMed  Google Scholar 

  • Tashima T, Nagatoishi S, Sagara H, Ohnuma S, Tsumoto K (2015) Osteomodulin regulates diameter and alters shape of collagen fibrils. Biochem Biophys Res Commun 463(3):292–296. doi:10.1016/j.bbrc.2015.05.053

    Article  CAS  PubMed  Google Scholar 

  • Tillgren V, Ho JC, Onnerfjord P, Kalamajski S (2015) The novel small leucine-rich protein chondroadherin-like (CHADL) is expressed in cartilage and modulates chondrocyte differentiation. J Biol Chem 290(2):918–925. doi:10.1074/jbc.M114.593541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tillgren V, Önnerfjord P, Haglund L, Heinegård D (2009) The tyrosine sulfate-rich domains of the LRR proteins fibromodulin and osteoadherin bind motifs of basic clusters in a variety of heparin-binding proteins, including bioactive factors. J Biol Chem 284(42):28543–28553. doi:10.1074/jbc.M109.047076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tio L, Martel-Pelletier J, Pelletier JP, Bishop PN, Roughley P, Farran A, Benito P, Monfort J (2014) Characterization of opticin digestion by proteases involved in osteoarthritis development. Joint Bone Spine 81(2):137–141. doi:10.1016/j.jbspin.2013.05.007

    Article  CAS  PubMed  Google Scholar 

  • Tomoeda M, Yamada S, Shirai H, Ozawa Y, Yanagita M, Murakami S (2008) PLAP-1/asporin inhibits activation of BMP receptor via its leucine-rich repeat motif. Biochem Biophys Res Commun 371(2):191–196. doi:10.1016/j.bbrc.2008.03.158

    Article  CAS  PubMed  Google Scholar 

  • Tompson SW, Merriman B, Funari VA, Fresquet M, Lachman RS, Rimoin DL, Nelson SF, Briggs MD, Cohn DH, Krakow D (2009) A recessive skeletal dysplasia, SEMD aggrecan type, results from a missense mutation affecting the C-type lectin domain of aggrecan. Am J Hum Genet 84(1):72–79. S0002-9297(08)00622-8 [pii]. doi:10.1016/j.ajhg.2008.12.001

    Google Scholar 

  • Troeberg L, Nagase H (2012) Proteases involved in cartilage matrix degradation in osteoarthritis. Biochim Biophys Acta 1824(1):133–145. doi:10.1016/j.bbapap.2011.06.020. S1570-9639(11)00195-6 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verzijl N, DeGroot J, Bank RA, Bayliss MT, Bijlsma JW, Lafeber FP, Maroudas A, TeKoppele JM (2001) Age-related accumulation of the advanced glycation endproduct pentosidine in human articular cartilage aggrecan: the use of pentosidine levels as a quantitative measure of protein turnover. Matrix Biol 20(7):409–417

    Article  CAS  PubMed  Google Scholar 

  • Vogel KG, Paulsson M, Heinegård D (1984) Specific inhibition of type I and type II collagen fibrillogenesis by the small proteoglycan of tendon. Biochem J 223(3):587–597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • von Marschall Z, Fisher LW (2010) Decorin is processed by three isoforms of bone morphogenetic protein-1 (BMP1). Biochem Biophys Res Commun 391(3):1374–1378. doi:10.1016/j.bbrc.2009.12.067

    Article  CAS  Google Scholar 

  • Wang Z, Weitzmann MN, Sangadala S, Hutton WC, Yoon ST (2013) Link protein N-terminal peptide binds to bone morphogenetic protein (BMP) type II receptor and drives matrix protein expression in rabbit intervertebral disc cells. J Biol Chem 288(39):28243–28253. doi:10.1074/jbc.M113.451948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watanabe H, Yamada Y (1999) Mice lacking link protein develop dwarfism and craniofacial abnormalities. Nat Genet 21(2):225–229

    Article  CAS  PubMed  Google Scholar 

  • Wendel M, Sommarin Y, Heinegard D (1998) Bone matrix proteins: isolation and characterization of a novel cell-binding keratan sulfate proteoglycan (osteoadherin) from bovine bone. J Cell Biol 141(3):839–847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiberg C, Hedbom E, Khairullina A, Lamandé SR, Oldberg Å, Timpl R, Mörgelin M, Heinegård D (2001) Biglycan and decorin bind close to the n-terminal region of the collagen VI triple helix. J Biol Chem 276(22):18947–18952. doi:10.1074/jbc.M100625200

    Article  CAS  PubMed  Google Scholar 

  • Wiberg C, Heinegård D, Wenglén C, Timpl R, Mörgelin M (2002) Biglycan organizes collagen VI into hexagonal-like networks resembling tissue structures. J Biol Chem 277(51):49120–49126. doi:10.1074/jbc.M206891200

    Article  CAS  PubMed  Google Scholar 

  • Wiberg C, Klatt AR, Wagener R, Paulsson M, Bateman JF, Heinegård D, Mörgelin M (2003) Complexes of matrilin-1 and biglycan or decorin connect collagen VI microfibrils to both collagen II and aggrecan. J Biol Chem 278(39):37698–37704. doi:10.1074/jbc.M304638200

    Article  CAS  PubMed  Google Scholar 

  • Williams DR Jr, Presar AR, Richmond AT, Mjaatvedt CH, Hoffman S, Capehart AA (2005) Limb chondrogenesis is compromised in the versican deficient hdf mouse. Biochem Biophys Res Commun 334(3):960–966. doi:10.1016/j.bbrc.2005.06.189

    Article  CAS  PubMed  Google Scholar 

  • Wilson R, Norris EL, Brachvogel B, Angelucci C, Zivkovic S, Gordon L, Bernardo BC, Stermann J, Sekiguchi K, Gorman JJ, Bateman JF (2012) Changes in the chondrocyte and extracellular matrix proteome during post-natal mouse cartilage development. Mol Cell Proteomics : MCP 11(1):M111.014159. doi:10.1074/mcp.M111.014159

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu F, Vij N, Roberts L, Lopez-Briones S, Joyce S, Chakravarti S (2007) A novel role of the lumican core protein in bacterial lipopolysaccharide-induced innate immune response. J Biol Chem 282(36):26409–26417. doi:10.1074/jbc.M702402200

    Article  CAS  PubMed  Google Scholar 

  • Xing D, Ma XL, Ma JX, Xu WG, Wang J, Yang Y, Chen Y, Ma BY, Zhu SW (2013) Association between aspartic acid repeat polymorphism of the asporin gene and susceptibility to knee osteoarthritis: a genetic meta-analysis. Osteoarthritis Cartilage 21(11):1700–1706. doi:10.1016/j.joca.2013.08.005

    Article  CAS  PubMed  Google Scholar 

  • Xu T, Bianco P, Fisher LW, Longenecker G, Smith E, Goldstein S, Bonadio J, Boskey A, Heegaard AM, Sommer B, Satomura K, Dominguez P, Zhao C, Kulkarni AB, Robey PG, Young MF (1998) Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice. Nat Genet 20(1):78–82. doi:10.1038/1746

    Article  CAS  PubMed  Google Scholar 

  • Yamaba S, Yamada S, Kajikawa T, Awata T, Sakashita H, Tsushima K, Fujihara C, Yanagita M, Murakami S (2015) PLAP-1/asporin regulates TLR2- and TLR4-induced inflammatory responses. J Dent Res. doi:10.1177/0022034515606859

    Google Scholar 

  • Yamaguchi Y, Mann DM, Ruoslahti E (1990) Negative regulation of transforming growth factor-beta by the proteoglycan decorin. Nature 346(6281):281–284. doi:10.1038/346281a0

    Article  CAS  PubMed  Google Scholar 

  • Zimmermann DR, Ruoslahti E (1989) Multiple domains of the large fibroblast proteoglycan, versican. EMBO J 8(10):2975–2981

    CAS  PubMed  PubMed Central  Google Scholar 

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Aspberg, A. (2016). Cartilage Proteoglycans. In: Grässel, S., Aszódi, A. (eds) Cartilage. Springer, Cham. https://doi.org/10.1007/978-3-319-29568-8_1

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