Abstract
Over the last decade, there have been several interesting advances in the treatment of osteoarthritis (OA), resulting in renewed interest in this field of medicine. Recent progress in the understanding of the pathophysiology of OA has facilitated the development of new drugs and treatments specifically aimed at effectively retarding the disease process. This chapter presents several new agents that have been introduced for the symptomatic treatment of OA. These medications have different mechanisms of action, some of which are not yet fully understood. Clinical studies are currently underway for some of those drugs to determine if they can exert structure-modifying effects to counteract the disease process. This chapter also reviews major fields of investigation that we believe hold promise for the near future.
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References
Cruz TF, Tang J, Pronost S, Pujol JP (1996) Molecular mechanisms implicated in the inhibition of collagenase expression by diacerhein. Rev Prat 46: S15–S19
Carney SL, Hicks CA, Tree B, Broadmore RJ (1995) An in vivo investigation of the effect of anthraquinones on the turnover of aggrecans in spontaneous osteoarthritis in the guinea pig. Inflamm Res 44: 182–186
Bendele AM, Bendele RA, Hulman JF, Swann BP (1996) Beneficial effects of treatment with diacerhein in guinea pigs with osteoarthritis. Rev Prat Ed Fr 46: S35–S39
Nguyen M, Dougados M, Berdah L, Amor B (1994) Diacerhein in the treatment of osteoarthritis of the hip. Arthritis Rheum 37: 529–536
Marcolongo R, Fioravanti A, Adami S, Tozzi E, Mian M, Zampieri A (1988) Efficacy and tolerability of diacerhein in the treatment of osteoarthritis. Curr Therap Res 43: 878–887
Mauviel A, Daireaux M, Hartmann DJ, Galera P, Loyau G, Pujol JP (1989) Effects of unsaponifiable extracts of avocado/soy beans (PIAS) on the production of collagen by cultures of synoviocytes, articular chondrocytes and skin fibroblasts. Rev Rhum Mai Osteoartic 56: 207–211
Henrotin Y, Labasse A, Jaspar JM, De Groote D, Zheng SX, Guillou B, Reginster JY (1998) Effects of three avocado/soybean unsaponifiable mixtures on metalloproteinases, cytokines and prostaglandin E2 production by human articular chondrocytes. Clin Rheumatol (In Press)
Maheu E, Mazieres B, Valat JP, Loyau G, Le Loet X, Bourgeois P, Grouin JM, Rozenberg S (1998) Symptomatic efficacy of avocado/soybean unsaponifiables in the treatment of osteoarthritis of the knee and hip: a prospective, randomized, double-blind, placebocontrolled, multicenter clinical trial with a six-month treatment period and a two- month follow-up demonstrating a persistent effect. Arthritis Rheum 41: 81–91
Blotman F, Maheu E, Wulwik A, Caspar H, Lopez A (1998) Efficacite et tolerance des insaponifiables d’avocat/soja dans le traitement de la gonarthrose et de la coxarthrose symptomatique. Rev Rhum (In Press)
Bassleer C, Henrotin Y, Franchimont P (1992) In vitro evaluation of drugs proposed as chondroprotective agents. Int J Tissue React 14: 231–241
Müller-Fasbender H, Bach G, Haase W, Rovati LC, Setnikar I (1994) Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee. Osteoarthritis Cartilage 2: 61–69
Noack W, Fischer M, Förster KK, Rovati LC, Setnikar I (1994) Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis Cartilage 2: 51–59
Reichelt A, Forster KK, Fischer M, Rovati LC, Setnikar I (1994) Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee. A randomised, placebocontrolled, double-blind study. Arzneimittelforschung 44: 75–80
Talent JM, Gracy RW (1996) Pilot study of oral polymeric N-acetyl-D-glucosamine as a potential treatment for patients with osteoarthritis. Clin Ther 18: 1184–1190
Mazieres B, Loyou G, Menkes CJ, Valat JP, Dreiser RL, Chorlot J, Masounabe-Puyanne A (1992) La chondroitine sulfate dans le traitement de la gonarthrose et de la coxarthose. Resultats a 5 mois d’une etude aveugle versus placebo. Rev Rhum Mal Osteoartic S9: 466–472
L’Hirondel J (1992) Klinische doppelblind-studie mit oral verabreichtem chondroitinsulfat gegen placebo bei der tibiofemoralen gonarthrose. Litera Rheumatologica 14: 77–84
Conrozier T, Vignon E (1992) Die wirkung von chondroitinsulfat bei der behandlug der hüftgelenksarthrose. Litera Rheumatologica 14: 69–75
Morreale P, Manopulo R, Galati M, Boccanera L, Saponati G, Bocchi L (1996) Comparison of the antiinflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis. J Rheumatol 23: 1385–1391
Bryant LR, des Rosier KF, Carpenter MT (1995) Hydroxychloroquine in the treatment of erosive osteoarthritis. J Rheumatol 22: 1527–1531
Mannoni A, Altman RD, Muniz OE, Serni U, Dean DD (1993) The effects of methotrexate on normal and osteoarthritic lapine articular cartilage. J Rheumatol 20: 849–855
Huskisson EC, Berry H, Gishen P, Jubb RW, Whitehead J (1995) Effects of antiinflammatory drugs on the progression of osteoarthritis of the knee. LINK Study Group. Longitudinal Investigation of Nonsteroidal Antiinflammatory Drugs in Knee Osteoarthritis. J Rheumatol 22: 1941–1946
Distel M, Mueller C, Bluhmki E, Fries J (1996) Safety of meloxicam: a global analysis of clinical trials. Br J Rheumatol 35 Suppl 1: 68–77
Bjarnason I, Macpherson A, Rotman H, Schupp J, Hayllar J (1997) A randomized, doubleblind, crossover comparative endoscopy study on the gastroduodenal tolerability of a highly specific cyclooxygenase-2 inhibitor, flosulide, and naproxen. Scand J Gastroenterol 32: 126–130
Zhao SZ, Hatoum H, Hubbard R, Koepp J, Dedhiya S, Geis S, Bocanegra T, Ware J, Keller S (1997) Effect of celecoxib, a novel COX-2 inhibitor, on health-related quality of life of patients with osteoarthritis of the knee. Arthritis Rheum 40 (Suppl): S88–S88 (Abstract)
Dieppe PA, Sathapatayavongs B, Jones HE, Bacon PA, Ring EF (1980) Intra-articular steroids in osteoarthritis. Rheum Rehabil 19: 212–217
Friedman DM, Moore ME (1980) The efficacy of intraarticular steroids in osteoarthritis: a double- blind study. J Rheumatol 7: 850–856
Valtonen EJ (1981) Clinical comparison of triamcinolonehexacetonide and betamethasone in the treatment of osteoarthrosis of the knee-joint. Scand J Rheumatol Suppl 41: 1–7
Balch HW, Gibson JM, El-Ghobarey AF, Bain LS, Lynch MP (1977) Repeated corticosteroid injections into knee joints. Rheum Rehabil 16: 137–140
Pelletier JP, Mineau F, Raynauld JP, Woessner JF Jr, Gunja-Smith Z, Martel-Pelletier J (1994) Intraarticular injections with methylprednisolone acetate reduce osteoarthritic lesions in parallel with chondrocyte stromelysin synthesis in experimental osteoarthritis. Arthritis Rheum 37 (3): 414–423
Namiki O, Toyoshima H, Morisaki N (1982) Therapeutic effect of intra-articular injection of high molecular weight hyaluronic acid on osteoarthritis of the knee. Int J Clin Pharm Ther Toxicol 20: 501–507
Bragantini A, Cassini M (1987) Controlled single-blind trial of intra-articulary injected hyaluronic acid in osteo-arthritis of the knee. Clin Trials Journal 24: 333–340
Dixon AS, Jacoby RK, Berry H, Hamilton EB (1988) Clinical trial of intra-articular injection of sodium hyaluronate in patients with osteoarthritis of the knee. Curr Med Res Opin 11: 205–213
Dougados M, Nguyen M, Listrat V, Amor B (1993) High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the knee: a 1 year placebo-controlled trial. Osteoarthritis Cartilage 1: 97–103
Leardini G, Mattara L, Franceschini M, Perbellini A (1991) Intra-articular treatment of knee osteoarthritis. A comparative study between hyaluronic acid and 6-methyl prednisolone acetate. Clin Exp Rheumatol 9: 375–381
Pietrogrande V, Melanotte PL, D’Agnolo B, Ulivi M, Benigni GA, Turchetto L, Pierfederici P, Perbellini A (1991) Hyaluronic acid versus methylprednisolone intra-articularly injected for the treatment of osteoarthritis of the knee. Curr Therap Res 50: 691–701
Jones AC, Pattrick M, Doherty S, Doherty M (1995) Intra-articular hyaluronic acid compared to intra-articular triamcinolone hexacetonide in inflammatory knee osteoarthritis. Osteoarthritis Cartilage 3: 269–273
Lohmander LS, Dalen N, Englund G, Hamalainen M, Jensen EM, Karlsson K, Odensten M, Ryd L, Sernbo I, Suomalainen O et al. (1996) Intra-articular hyaluronan injections in the treatment of osteoarthritis of the knee: a randomised, double blind, placebo controlled multicentre trial. Hyaluronan Multicentre Trial Group. Ann Rheum Dis 55: 424–431
Grecomoro G, Piccione F, Letizia G (1992) Therapeutic synergism between hyaluronic acid and dexamethasone in the intra-articular treatment of osteoarthritis of the knee: a preliminary open study. Curr Med Res Opin 13: 49–55
Listrat V, Ayral X, Patarnello F, Bonvarlet JP, Simonnet J, Amor B, Dougados M (1997) Arthroscopic evaluation of potential structure modifying activity of hyaluronan (Hyalgan) in osteoarthritis of the knee. Osteoarthritis Cartilage 5: 153–160
Scale D, Wobig M, Wolpert W (1994) Viscosupplementation of osteoarthritic knees with hylan: a treatment schedule study. Curr Therap Res 55: 220–232
Adams ME, Atkinson MH, Lussier AJ, Schulz JI, Siminovitch KA, Wade JP, Zummer M (1995) The role of viscosupplementation with hylan G-F 20 (Synvisc) in the treatment of osteoarthritis of the knee: a Canadian multicenter trial comparing hylan G-F 20 alone, hylan G-F 20 with non-steroidal anti- inflammatory drugs (NSAIDs) and NSAIDs alone. Osteoarthritis Cartilage 3: 213–225
Lussier A, Cividino AA, McFarlane CA, Olszynski WP, Potashner WJ, De Medicis R (1996) Viscosupplementation with hylan for the treatment of osteoarthritis: findings from clinical practice in Canada. J Rheumatol 23: 1579–1585
Vacha J, Pesakova V, Krajickova J, Adam M (1984) Effect of glycosaminoglycan polysulphate on the metabolism of cartilage ribonucleic acid. Arzneimittelforschung 34: 607–609
Pavelka K Jr, Sedlackova M, Gatterova J, Becvar R, Pavelka K (1995) Glycosaminoglycan polysulfuric acid (GAGPS) in osteoarthritis of the knee. Osteoarthritis Cartilage 3: 15–23
Grinnell F (1994) Fibroblasts, myofibroblasts, and wound contraction. J Cell Biol 124: 401–404
Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331: 889–895
Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI, Goldberg VM (1994) Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am 76: 579–592
Hommings GN, Bulstra SK, Bouwmeester PS, van der Linden AJ (1990) Perichondral grafting for cartilage lesions of the knee. J Bone Joint Surg [Br ] 72: 1003–1007
Kreder HJ, Moran M, Keeley FW, Salter RB (1994) Biologic resurfacing of a major joint defect with cryopreserved allogeneic periosteum under the influence of continuous passive motion in a rabbit model. Clin Orthop 288–296
Girdler NM (1993) Repair of articular defects with autologous mandibular condylar cartilage. J Bone Joint Surg [Br] 75: 710–714
Malinin TI, Mnaymneh W, Lo HK, Hinkle DK (1994) Cryopreservation of articular cartilage. Ultrastructural observations and long-term results of experimental distal femoral transplantation. Clin Orthop 18–32
Vacanti CA, Kim W, Schloo B, Upton J, Vacanti JP (1994) Joint resurfacing with cartilage grown in situ from cell-polymer structures. Am J Sports Med 22: 485–488
Hendrickson DA, Nixon AJ, Grande DA, Todhunter RJ, Minor RM, Erb H, Lust G (1994) Chondrocyte-fibrin matrix transplants for resurfacing extensive articular cartilage defects. J Orthop Res
Nixon AJ, Sams AE, Lust G, Grande D, Mohammed HO (1993) Temporal matrix synthesis and histologic features of a chondrocyte-laden porous collagen cartilage analogue. Am J Vet Res 54: 349–356
Freed LE, Marquis JC, Nohria A, Emmanual J, Mikos AG, Langer R (1993) Neocartilage formation in vitro and in vivo using cells cultured on synthetic biodegradable polymers. J Biomed Mater Res 27: 11–23
Messner K (1994) Durability of artificial implants for repair of osteochondral defects of the medial femoral condyle in rabbits. Biomaterials 15: 657–664
Messner K, Gillquist J (1993) Synthetic implants for the repair of osteochondral defects of the medial femoral condyle: a biomechanical and histological evaluation in the rabbit knee. Biomaterials 14: 513–521
Burmester GR, Perka C, Sittinger M (1997) Tissue engineering: New ways to treat joint destruction in the next millenium. Proceedings of the EULAR Meeting S: 288: 71
Lafeber FPJG, van Roy HL, Van der Kraan PM, van den Berg WB, Bijlsma JW (1997) Transforming growth factor-beta predominantly stimulates phenotypically changed chondrocytes in osteoarthritic human cartilage. J Rheumatol 24: 536–542
van den Berg WB (1995) Growth factors in experimental osteoarthritis: transforming growth factor beta pathogenic? J Rheum Suppl 43: 143–145
Rogachefsky RA, Dean DD, Howell DS, Altman RD (1993) Treatment of canine osteoarthritis with insulin-like growth factor-1 (IGF-1) and sodium pentosan polysulfate. Osteoarthritis Cartilage 1: 105–114
Dinarello CA (1996) Biologic basis for interleukin-1 in disease. Blood 87 (6): 2095–2147
Arend WP (1993) Interleukin-1 receptor antagonist. [Review] Adv Immunol 54: 167–227
Jovanovic D, Pelletier JP, Alaaeddine N, Mineau F, Geng C, Ranger P, Martel-Pelletier J (1998) Effect of IL-13 on cytokines, cytokine receptors and inhibitors on human osteoarthritic synovium and synovial fibroblasts. Osteoarthritis Cartilage 6: 10–18
Bendrups A, Hilton A, Meager A, Hamilton JA (1993) Reduction of tumor necrosis factor alpha and interleukin-1 beta levels in human synovial tissue by interleukin-4 and glucocorticoid. Rheumatol Int 12: 217–220
Katsikis PD, Chu CQ, Brennan FM, Maini RN, Feldmann M (1994) Immunoregulatory role of interleukin-10 in rheumatoid arthritis. J Exp Med 179: 1517–1527
Hart PH, Ahern MJ, Smith MD, Finlay-Jones JJ (1995) Regulatory effects of IL-13 on synovial fluid macrophages and blood monocytes from patients with inflammatory arthritis. Clin Exp Immunol 99: 331–337
Defrance T, Carayon P, Billian G, Guillemot J-C, Minty A, Caput D, Ferrara P (1994) Interleukin-13 is a B cell stimulating factor. J Exp Med 179: 135–143
de Waal Malefyt R, Figdor CG, Huijbens R, Mohan-Peterson S, Bennett B, Culpepper JA, Dang W, Zurawski G, de Vries JE (1993) Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10. J Immunol 151: 6370–6381
Arend WP, Dayer JM (1995) Inhibition of the production and effects of interleukin-1 and tumor necrosis factor alpha in rheumatoid arthritis. Arthritis Rheum 38: 252–160
Evans CH, Robbins PD (1994) Gene therapy for arthritis. In: Wolff J A (eds) Gene Therapeutics: Methods and Applications of Direct Gene Transfer. Birkhauser, Boston, pp 320–343
Chernajovsky Y, Feldmann M, Maini RN (1995) Gene therapy of rheumatoid arthritis via cytokine regulation: future perspectives. Br Med Bull 51: 503–516
Pelletier JP, Martel-Pelletier J, Howell DS (1997) Etiopathogenesis of osteoarthritis. In: Koopman W J (eds) Arthritis and Allied Conditions. A Textbook of Rheumatology. 13th edn Williams & Wilkins, Baltimore, pp 1969–1984.
Caron JP, Fernandes JC, Martel-Pelletier J, Tardif G, Mineau F, Geng C, Pelletier JP (1996) Chondroprotective effect of intraarticular injections of interleukin-1 receptor antagonist in experimental osteoarthritis: suppression of collagenase-1 expression. Arthritis Rheum 39: 1535–1544
Müller-Ladner U, Roberts CR, Franklin BN, Gay RE, Robbins PD, Evans CH, Gay S (1997) Human IL-1Ra gene transfer into human synovial fibroblasts is chondroprotective. J Immunol 158: 3492–3498
Pelletier JP, Caron JP, Evans CH, Robbins PD, Georgescu HI, Jovanovic D, Fernandes JC, Martel-Pelletier J (1997) In vivo suppression of early experimental osteoarthritis by ILRa using gene therapy. Arthritis Rheum 40: 1012–1019
Baragi VM, Renkiewicz RR, Jordan H, Bonadio J, Harman JW, Roessler BJ (1995) Transplantation of transduced chondrocytes protects articular cartilage from interleukin-1- induced extracellular matrix degradation. J Clin Invest 96: 2454–2460
Tomita T, Hashimoto H, Tomita N, Morishita R, Lee SB, Hayashida K, Nakamura N, Yonenobu K, Kaneda Y, Ochi T (1997) In vivo direct gene transfer into articular cartilage by intraarticular injection mediated by HVJ (sendai virus) and liposomes. Arthritis Rheum 40 (5): 901–906
Pelletier JP, Di Battista JA, Roughley PJ, McCollum R, Martel-Pelletier J (1993) Cytokines and inflammation in cartilage degradation. In: Moskowitz R W (eds) Osteoarthritis, Edition of Rheumatic Disease Clinics of North America. W.B. Saunders Company, Philadelphia, pp 545–568.
Martel-Pelletier J, Mineau F, Tardif G, Fernandes JC, Ranger P, Loose L, Pelletier JP (1996) Tenidap reduces the level of interleukin-1 receptors and collagenase expression in human arthritic synovial fibroblasts. J Rheumatol 23: 24–31
Fernandes JC, Martel-Pelletier J, Otterness IG, Lopez-Anaya A, Mineau F, Tardif G, Pelletier JP (1995) Effects of tenidap on canine experimental osteoarthritis: I. Morphologic and metalloprotease analysis. Arthritis Rheum 38: 1290–1303
Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D, McNulty D, Blumenthal MJ, Heys RJ, Landvatter SW et al. (1994) A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 372: 739
Ridley SH, Sarsfield SJ, Lee JC, Bigg HF, Cawston TE, Taylor DJ, DeWitt DL, Saklatvala J (1997) Actions of IL-1 are selectively controlled by P38 mitogen-activated protein kinease regulation of prostaglandin H synthase-2, metalloproteinases, and IL-6 at different levels. J Immunol 158: 3165–3173
Fujiwara T, Grimm EA (1992) Specific inhibition of interleukin-1 beta gene expression by an antisense oligonucleotide: obligatory role of interleukin-1 in the generation of lymphokine-activated killer cells. Cancer Res 52 (18): 14954–4959
Manson J, Brown T, Duff G (1990) Modulation of interleukin-1 beta gene expression using antisense phosphorothioate oligonucleotides. Lymphokine Res 9: 35–42
Cerretti DP, Kozlosky CJ, Mosley B, Nelson N, Van Ness K, Greenstreet TA, March CJ, Kronheim SR, Druck T, Cannizzaro LA (1992) Molecular cloning of the interleukin-1 beta converting enzyme. Science 256: 97–100
Stosic-Grujicic S, Basara N, Milenkovic P, Dinarello CA (1995) Modulation of acute myeloblasts leukemia (AML) cell proliferation and blast colony formation by antisense oligomer for IL-1 beta converting enzyme (ICE) and IL-1 receptor antagonist (IL-1ra). J Chemother 7: 67–70
Ku G, Faust T, Lauffer LL, Livingston DJ, Harding MW (1996) Interleukin-1ß converting enzyme inhibition blocks progression of the type II collagen-induced arthritis in mice. Cytokine 8: 377–386
Burger D, Chicheportiche R, Giri JG, Dayer JM (1995) The inhibitory activity of human interleukin-1 receptor antagonist is enhanced by type II interleukin-1 soluble receptor and hindered by type I interleukin-1 soluble receptor. J Clin Invest 96: 38–41
Joosten LA, Helsen MM, van de Loo FA, van den Berg WB (1996) Anticytokine treatment of established type II collagen-induced arthritis in DBA/1 mice. A comparative study using anti-TNF alpha, anti- IL-1 alpha/beta, and IL-1Ra. Arthritis Rheum 39: 797–809
Westacott CI, Atkins RM, Dieppe PA, Elson CJ (1994) Tumour necrosis factor-alpha receptor expression on chondrocytes isolated from human articular cartilage. J Rheumatol 21: 1710–1715
Martel-Pelletier J, Mineau F, Jolicoeur FC, Pelletier JP (1995) Modulation of TNFsR55 and TNFsR75 by cytokines and growth factors in human synovial fibroblasts. J Rheumatol 22: 115–119
Williams RO, Ghrayeb J, Feldmann M, Maini RN (1995) Successful therapy of collageninduced arthritis with TNF receptor-IgG fusion protein and combination with anti-CD4. Immunology 84: 433–439
Elliott MJ, Maini RN, Feldmann M, Kalden JR, Antoni C, Smolen JS, Leeb B, Breedveld FC, Macfarlane JD, Bijl H (1994) Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 344: 1105–1110
Evans CH, Stefanovic-Racic M, Lancaster J (1995) Nitric oxide and its role in orthopaedic disease. Clin Orthop 312: 275–294
Mclnnes IB, Leung BP, Field M, Wei XQ, Huang FP, Sturrock RD, Kinninmonth A, Weidner J, Mumford R, Liew FY (1996) Production of nitric oxide in the synovial membrane of rheumatoid and osteoarthritis patients. J Exp Med 184: 1519–1524
Nathan C (1997) Inducible nitric oxide synthase: what difference does it make? J Clin Invest 100: 2417–2423
Pelletier JP, Mineau F, Ranger P, Tardif G, Martel-Pelletier J (1996) The increased synthesis of inducible nitric oxide inhibits IL-1Ra synthesis by human articular chondrocytes: possible role in osteoarthritic cartilage degradation. Osteoarthritis Cartilage 4: 77–84
Jarvinen TAH, Moilanen T, Järvinen TLN, Moilanen E (1995) Nitric oxide mediates in terleukin-1 induced inhibition of glycosaminoglycan synthesis in rat articular cartilage. Mediators of Inflammation 4: 107–111
Murrell GAC, Jang D, Williams RJ (1995) Nitric oxide activates metalloprotease enzymes in articular cartilage. Biochem Biophys Res Commun 206: 15–21
Farrell AJ, Blake DR, Palmer RM, Moncada S (1992) Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Ann Rheum Dis 51: 1219–1222
Grabowski PS, Wright PK, Van’t Hof RJ, Helfrich MH, Ohshima H, Ralston SH (1997) Immunolocalization of inducible nitric oxide synthase in synovium and cartilage in rheumatoid arthritis and osteoarthritis. Br J Rheumatol 36: 651–655
Amin AR, Di Cesare PE, Vyas P, Attur MG, Tzeng E, Billiar TR, Stuchin S, Abramson SB (1995) The expression and regulation of nitric oxide synthase in human osteoarthritis- affected chondrocytes: evidence for an inducible “neuronal-like” nitric oxide synthase. J Exp Med 182: 2097–2102
Stefanovic-Racic M, Stadler J, Evans CH (1993) Nitric oxide and arthritis. Arthritis Rheum 36: 1036–1044
Connor JR, Manning PT, Settle SL, Moore WM, Jerome GM, Webber RK, Tjoeng FS, Currie MG (1995) Suppression of adjuvant-induced arthritis by selective inhibition of inducible nitric oxide synthase. Eur J Pharmacol 273: 15–24
Stefanovic-Racic M, Meyers K, Meschter C, Coffey JW, Hoffman RA, Evans CH (1994) N- monomethyl arginine, an inhibitor of nitric oxide synthase, suppresses the development of adjuvant arthritis in rats. Arthritis Rheum 37: 1062–1069
Stefanovic-Racic M, Meyers K, Meschter C, Coffey JW, Hoffman RA, Evans CH (1995) Comparison of the nitric oxide synthase inhibitors methylarginine and aminoguanidine as prophylactic and therapeutic agents in rat adjuvant arthritis. J Rheumatol 22: 1922–1928
McCartney-Francis N, Allen JB, Mizel DE, Albina JE, Xie Q, Nathan DF, Wahl SM (1993) Suppression of arthritis by an inhibitor of nitric oxide synthase. J Exp Med 178: 749–754
Pelletier JP, Jovanovic D, Fernandes JC, Manning PT, Connor JR, Currie MG, Di Battista JA, Martel-Pelletier J (1998) Selective inhibition of inducible nitric oxide synthase reduces in vivo the progression of experimental osteoarthritis. Arthritis Rheum (in press)
Dean DD (1991) Proteinase-mediated cartilage degradation in osteoarthritis. Semin Arthritis Rheum 20: 2–11
Martel-Pelletier J, Pelletier JP (1996) Wanted — the collagenase responsible for the destruction of the collagen network in human cartilage. Br J Rheumatol 35: 818–820
Vincenti MP, Clark IM, Brinckerhoff CE (1994) Using inhibitors of metalloproteinases to treat arthritis. Easier said than done? [Review]. Arthritis Rheum 37: 1115–1126
Yu LP Jr, Smith GN Jr, Brandt KD, Myers SL, O’Connor BL, Brandt DA (1992) Reduction of the severity of canine osteoarthritis by prophylactic treatment with oral doxycycline. Arthritis Rheum 35: 1150–1159
MacPherson LJ, Bayburt EK, Capparelli MP, Carroll BJ, Goldstein R, Justice MR, Zhu L, Hu S, Melton RA, Fryer L et al. (1997) Discovery of CGS 27023 A, a non-peptidic, potent, and orally active stromelysin inhibitor that blocks cartilage degradation in rabbits. J Med Chem 40: 2525–2532
Lewis EJ, Bishop J, Bottomley KM, Bradshaw D, Brewster M, Broadhurst MJ, Brown PA, Budd JM, Elliott L, Greenham AK et al. (1997) Ro 32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitro and in vivo. Br J Pharmacol 121: 540–546
DiMartino M, Wolff C, High W, Stroup G, Hoffman S, Laydon J, Lee JC, Bertolini D, Galloway WA, Crimmin MJ et al. (1997) Anti-arthritic activity of hydroxamic acid-based pseudopeptide inhibitors of matrix metalloproteinases and TNF alpha processing. Inflamm Res 46: 211–215
Hirayama R, Yamamoto M, Tsukida T, Matsuo K, Obata Y, Sakamoto F, Ikeda S (1997) Synthesis and biological evaluation of orally active matrix metalloproteinase inhibitors. Bioorg Med Chem 5: 765–778
Vincenti MP, White LA, Schroen DJ, Benbow U, Brinckerhoff CE (1996) Regulating expression of the gene for matrix metalloproteinase-1 (collagenase): mechanisms that control enzyme activity, transcription, and mRNA stability. Crit Rev Eukaryot Gene Exp 6: 391–411
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Pelletier, J.P., Haraoui, B., Fernandes, J.C. (1999). New and Future Therapies for Osteoarthritis. In: Osteoarthritis. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60026-5_20
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