Best Practice & Research Clinical Rheumatology
Volume 20, Issue 5 , Pages 1003-1025 , October 2006

Update on the biology of the chondrocyte and new approaches to treating cartilage diseases

  • Mary B. Goldring, PhD (Associate Professor)

      Affiliations

    • Corresponding Author InformationAddress: Harvard Institutes of Medicine, HIM 246, 4 Blackfan Circle, Boston, MA 02115-5713, USA. Tel.: +1 617 667 0742; Fax: +1 617 975 5299.

References 

  1. Harris ED. The bone and joint decade: a catalyst for progress. Arthritis and Rheumatism. 2001;44:1969–1970
  2. Felson DT. Risk factors for osteoarthritis: understanding joint vulnerability. Clinical Orthopaedics and Related Research. 2004;427(supplement):S16–S21
  3. Peach CA, Carr AJ, Loughlin J. Recent advances in the genetic investigation of osteoarthritis. Trends in Molecular Medicine. 2005;11:186–191
  4. Spencer JM, Loughlin J, Clipsham K, et al. Genetic background increases the risk of hip osteoarthritis. Clinical Orthopaedics and Related Research. 2005;134–137
  5. Valdes AM, Van Oene M, Hart DJ, et al. Reproducible genetic associations between candidate genes and clinical knee osteoarthritis in men and women. Arthritis and Rheumatism. 2006;54:533–539
  6. Hunter DJ, Zhang Y, Niu J, et al. Structural factors associated with malalignment in knee osteoarthritis: the Boston osteoarthritis knee study. The Journal of Rheumatology. 2005;32:2192–2199
  7. Lee JH, Fitzgerald JB, Dimicco MA, et al. Mechanical injury of cartilage explants causes specific time-dependent changes in chondrocyte gene expression. Arthritis and Rheumatism. 2005;52:2386–2395
  8. Loeser RF. Aging cartilage and osteoarthritis – what's the link?. Science of Aging Knowledge Environment. 2004;2004(29):pe31
  9. Carrington JL. Aging bone and cartilage: cross-cutting issues. Biochemical and Biophysical Research Communications. 2005;328:700–708
  10. Wieland HA, Michaelis M, Kirschbaum BJ, et al. Osteoarthritis – an untreatable disease?. Nature Reviews. Drug Discovery. 2005;4:331–344
  11. Solomon SD, McMurray JJ, Pfeffer MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. The New England Journal of Medicine. 2005;352:1071–1080
  12. Brandt KD, Mazzuca SA. Lessons learned from nine clinical trials of disease-modifying osteoarthritis drugs. Arthritis and Rheumatism. 2005;52:3349–3359
  13. Wilkins RJ, Browning JA, Ellory JC. Surviving in a matrix: membrane transport in articular chondrocytes. The Journal of Membrane Biology. 2000;177:95–108
  14. Mobasheri A, Richardson S, Mobasheri R, et al. Hypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3: putative molecular components of the oxygen and glucose sensing apparatus in articular chondrocytes. Histology and Histopathology. 2005;20:1327–1338
  15. Poole AR. Cartilage in health and disease. In:  Koopman W editors. Arthritis and Allied Conditions: A Textbook of Rheumatology. 15th edn. Philadelphia: Lippincott, Williams, and Wilkins; 2005;p. 223–269
  16. Goldring SR, Goldring MB. Chapter 1: Biology of the normal joint. In:  Harris ED,  Ruddy S,  Sledge CB,  Sergent JS,  Budd RC editor. Kelley's Textbook of Rheumatology. 7th edn.. Philadelphia: WB Saunders; 2004;p. 1–34
  17. Poole AR, Kojima T, Yasuda T, et al. Composition and structure of articular cartilage: a template for tissue repair. Clinical Orthopaedics. 2001;391(supplement):S26–S33
  18. Struglics A, Larsson S, Pratta MA, et al. Human osteoarthritis synovial fluid and joint cartilage contain both aggrecanase- and matrix metalloproteinase-generated aggrecan fragments. Osteoarthritis and Cartilage. 2006;14:101–113
  19. Tetlow LC, Adlam DJ, Woolley DE. Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage. Arthritis and Rheumatism. 2001;44:585–594
  20. Wu W, Billinghurst RC, Pidoux I, et al. Sites of collagenase cleavage and denaturation of type II collagen in aging and osteoarthritic articular cartilage and their relationship to the distribution of matrix metalloproteinase 1 and matrix metalloproteinase 13. Arthritis and Rheumatism. 2002;46:2087–2094
  21. Guilak F, Fermor B, Keefe FJ, et al. The role of biomechanics and inflammation in cartilage injury and repair. Clinical Orthopaedics and Related Research. 2004;423:17–26
  22. Homandberg GA. Cartilage damage by matrix degradation products: fibronectin fragments. Clinical Orthopaedics and Related Research. 2001;391(supplement):S100–S107
  23. Pritzker KP, Gay S, Jimenez SA, et al. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis and Cartilage. 2006;14:13–29
  24. Hermansson M, Sawaji Y, Bolton M, et al. Proteomic analysis of articular cartilage shows increased type II collagen synthesis in osteoarthritis and expression of inhibin betaA (activin A), a regulatory molecule for chondrocytes. The Journal of Biological Chemistry. 2004;279:43514–43521
  25. Aigner T, Bartnik E, Sohler F, et al. Functional genomics of osteoarthritis: on the way to evaluate disease hypotheses. Clinical Orthopaedics and Related Research. 2004;427(supplement):S138–S143
  26. Fukui N, Zhu Y, Maloney WJ, et al. Stimulation of BMP-2 expression by pro-inflammatory cytokines IL-1 and TNF-α in normal and osteoarthritic chondrocytes. The Journal of Bone and Joint Surgery. American Volume. 2003;85-A(supplement 3):59–66
  27. Tchetina EV, Squires G, Poole AR. Increased type II collagen degradation and very early focal cartilage degeneration is associated with upregulation of chondrocyte differentiation related genes in early human articular cartilage lesions. The Journal of Rheumatology. 2005;32:876–886
  28. Aigner T, Gebhard PM, Schmid E, et al. SOX9 expression does not correlate with type II collagen expression in adult articular chondrocytes. Matrix Biology. 2003;22:363–372
  29. Aigner T, Rose J, Martin J, et al. Aging theories of primary osteoarthritis: from epidemiology to molecular biology. Rejuvenation Research. 2004;7:134–145
  30. Goldring SR, Goldring MB. The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clinical Orthopaedics. 2004;427(supplement):S27–S36
  31. Goldring MB, Berenbaum F. The regulation of chondrocyte function by proinflammatory mediators: prostaglandins and nitric oxide. Clinical Orthopaedics. 2004;427(supplement):S37–S46
  32. Benito MJ, Veale DJ, FitzGerald O, et al. Synovial tissue inflammation in early and late osteoarthritis. Annals of the Rheumatic Diseases. 2005;64:1263–1267
  33. Malemud CJ. Cytokines as therapeutic targets for osteoarthritis. BioDrugs. 2004;18:23–35
  34. Evans CH. Novel biological approaches to the intra-articular treatment of osteoarthritis. BioDrugs. 2005;19:355–362
  35. Borzi RM, Mazzetti I, Marcu KB, et al. Chemokines in cartilage degradation. Clinical Orthopaedics and Related Research. 2004;427(supplement):S53–S61
  36. Lubberts E, Koenders MI, van den Berg WB. The role of T cell interleukin-17 in conducting destructive arthritis: lessons from animal models. Arthritis Research and Therapy. 2005;7:29–37
  37. Barksby HE, Hui W, Wappler I, et al. Interleukin-1 in combination with oncostatin M up-regulates multiple genes in chondrocytes: implications for cartilage destruction and repair. Arthritis and Rheumatism. 2006;54:540–550
  38. Denko CW, Malemud CJ. Role of the growth hormone/insulin-like growth factor-1 paracrine axis in rheumatic diseases. Seminars in Arthritis and Rheumatism. 2005;35:24–34
  39. Bobacz K, Gruber R, Soleiman A, et al. Expression of bone morphogenetic protein 6 in healthy and osteoarthritic human articular chondrocytes and stimulation of matrix synthesis in vitro. Arthritis and Rheumatism. 2003;48:2501–2508
  40. Chubinskaya S, Kumar B, Merrihew C, et al. Age-related changes in cartilage endogenous osteogenic protein-1 (OP-1). Biochimica et Biophysica Acta. 2002;1588:126–134
  41. Blaney Davidson EN, Scharstuhl A, Vitters EL, et al. Reduced transforming growth factor-beta signaling in cartilage of old mice: role in impaired repair capacity. Arthritis Research and Therapy. 2005;7:R1338–R1347
  42. Loeser RF, Pacione CA, Chubinskaya S. The combination of insulin-like growth factor 1 and osteogenic protein 1 promotes increased survival of and matrix synthesis by normal and osteoarthritic human articular chondrocytes. Arthritis and Rheumatism. 2003;48:2188–2196
  43. Loeser RF, Chubinskaya S, Pacione C, et al. Basic fibroblast growth factor inhibits the anabolic activity of insulin-like growth factor 1 and osteogenic protein 1 in adult human articular chondrocytes. Arthritis and Rheumatism. 2005;52:3910–3917
  44. Iwanaga H, Matsumoto T, Enomoto H, et al. Enhanced expression of insulin-like growth factor-binding proteins in human osteoarthritic cartilage detected by immunohistochemistry and in situ hybridization. Osteoarthritis and Cartilage. 2005;13:439–448
  45. De Ceuninck F, Caliez A, Dassencourt L, et al. Pharmacological disruption of insulin-like growth factor 1 binding to IGF-binding proteins restores anabolic responses in human osteoarthritic chondrocytes. Arthritis Research and Therapy. 2004;6:R393–R403
  46. Smeets RL, Veenbergen S, Arntz OJ, et al. A novel role for SOCS3 in cartilage destruction via induction of chondrocyte desnesitization towards IGF-1. Arthritis and Rheumatism. 2006;54(5):1518–1528
  47. Wang J, Elewaut D, Veys EM, et al. Insulin-like growth factor 1-induced interleukin-1 receptor II overrides the activity of interleukin-1 and controls the homeostasis of the extracellular matrix of cartilage. Arthritis and Rheumatism. 2003;48:1281–1291
  48. Takahashi N, Rieneck K, van der Kraan PM, et al. Elucidation of IL-1/TGF-beta interactions in mouse chondrocyte cell line by genome-wide gene expression. Osteoarthritis and Cartilage. 2005;13:426–438
  49. Moulharat N, Lesur C, Thomas M, et al. Effects of transforming growth factor-beta on aggrecanase production and proteoglycan degradation by human chondrocytes in vitro. Osteoarthritis and Cartilage. 2004;12:296–305
  50. Kaiser M, Haag J, Soder S, et al. Bone morphogenetic protein and transforming growth factor beta inhibitory Smads 6 and 7 are expressed in human adult normal and osteoarthritic cartilage in vivo and are differentially regulated in vitro by interleukin-1beta. Arthritis and Rheumatism. 2004;50:3535–3540
  51. Blaney Davidson EN, Vitters EL, van der Kraan PM, et al. Expression of TGF-beta and the TGF-beta signaling molecule SMAD-2P in spontaneous and instability-induced osteoarthritis. Role in cartilage degradation, chondrogenesis and osteophyte formation. Annals of the Rheumatic Diseases. 2006;[E-pub Jan 26]
  52. Goldring MB, Tsuchimochi K, Ijiri K. The control of chondrogenesis. Journal of Cellular Biochemistry. 2006;97:33–44
  53. Gruber R, Mayer C, Bobacz K, et al. Effects of cartilage-derived morphogenetic proteins and osteogenic protein-1 on osteochondrogenic differentiation of periosteum-derived cells. Endocrinology. 2001;142:2087–2094
  54. Majumdar MK, Wang E, Morris EA. BMP-2 and BMP-9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and overcomes the inhibitory effect of IL-1. Journal of Cellular Physiology. 2001;189:275–284
  55. Chubinskaya S, Kuettner KE. Regulation of osteogenic proteins by chondrocytes. The International Journal of Biochemistry and Cell Biology. 2003;35:1323–1340
  56. Grunder T, Gaissmaier C, Fritz J, et al. Bone morphogenetic protein (BMP)-2 enhances the expression of type II collagen and aggrecan in chondrocytes embedded in alginate beads. Osteoarthritis and Cartilage. 2004;12:559–567
  57. Ornitz DM. FGF signaling in the developing endochondral skeleton. Cytokine and Growth Factor Reviews. 2005;16:205–213
  58. Trippel SB. Growth factor inhibition: potential role in the etiopathogenesis of osteoarthritis. Clinical Orthopaedics and Related Research. 2004;427(supplement):S47–S52
  59. Vincent T, Hermansson M, Bolton M, et al. Basic FGF mediates an immediate response of articular cartilage to mechanical injury. Proceedings of the National Academy of Sciences of the USA. 2002;99:8259–8264
  60. Vincent TL, Hermansson MA, Hansen UN, et al. Basic fibroblast growth factor mediates transduction of mechanical signals when articular cartilage is loaded. Arthritis and Rheumatism. 2004;50:526–533
  61. Ellsworth JL, Berry J, Bukowski T, et al. Fibroblast growth factor-18 is a trophic factor for mature chondrocytes and their progenitors. Osteoarthritis and Cartilage. 2002;10:308–320
  62. Au A, Polotsky A, Krzyminski K, et al. Evaluation of thermoreversible polymers containing fibroblast growth factor 9 (FGF-9) for chondrocyte culture. Journal of Biomedical Materials Research A. 2004;69:367–372
  63. Shimoaka T, Ogasawara T, Yonamine A, et al. Regulation of osteoblast, chondrocyte, and osteoclast functions by fibroblast growth factor (FGF)-18 in comparison with FGF-2 and FGF-10. The Journal of Biological Chemistry. 2002;277:7493–7500
  64. Moore EE, Bendele AM, Thompson DL, et al. Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. Osteoarthritis and Cartilage. 2005;13:623–631
  65. Solomon DH. Selective cyclooxygenase 2 inhibitors and cardiovascular events. Arthritis and Rheumatism. 2005;52:1968–1978
  66. McAlindon TE, Biggee BA. Nutritional factors and osteoarthritis: recent developments. Current Opinion in Rheumatology. 2005;17:647–652
  67. Uitterlinden EJ, Jahr H, Koevoet JL, et al. Glucosamine decreases expression of anabolic and catabolic genes in human osteoarthritic cartilage explants. Osteoarthritis and Cartilage. 2005;14(3):250–257
  68. Clegg DO, Reda DJ, Harris CL, et al. The efficacy of glucosamine and chondroitin sulfate in patients with painful knee osteoarthritis (OA): the glucosamine/chondroitin arthritis intervention trial (GAIT). Arthritis and Rheumatism. 2005;52(supplement):S256
  69. Braddock M, Quinn A. Targeting IL-1 in inflammatory disease: new opportunities for therapeutic intervention. Nature Reviews. Drug Discovery. 2004;3:330–339
  70. Murphy G, Lee MH. What are the roles of metalloproteinases in cartilage and bone damage?. Annals of the Rheumatic Diseases. 2005;64(supplement 4):iv44–iv47
  71. Brandt KD, Mazzuca SA, Katz BP, et al. Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebo-controlled, double-blind trial. Arthritis and Rheumatism. 2005;52:2015–2025
  72. Boyle DL, Kowaluk EA, Jarvis MF, et al. Anti-inflammatory effects of ABT-702, a novel non-nucleoside adenosine kinase inhibitor, in rat adjuvant arthritis. The Journal of Pharmacology and Experimental Therapeutics. 2001;296:495–500
  73. Chevalier X, Giraudeau B, Conrozier T, et al. Safety study of intraarticular injection of interleukin 1 receptor antagonist in patients with painful knee osteoarthritis: a multicenter study. The Journal of Rheumatology. 2005;32:1317–1323
  74. Frisbie DD, Ghivizzani SC, Robbins PD, et al. Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene. Gene Therapy. 2002;9:12–20
  75. Glasson S. Identification of targets through histologic evaluation of osteoarthritis in knockout mice. Osteoarthritis and Cartilage. 2005;13(supplement A):S3
  76. Rudolphi K, Gerwin N, Verzijl N, et al. Pralnacasan, an inhibitor of interleukin-1beta converting enzyme, reduces joint damage in two murine models of osteoarthritis. Osteoarthritis and Cartilage. 2003;11:738–746
  77. Blom AB, van Lent PL, Holthuysen AE, et al. Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritis. Osteoarthritis and Cartilage. 2004;12:627–635
  78. de Hooge AS, van de Loo FA, Bennink MB, et al. Male IL-6 gene knock out mice developed more advanced osteoarthritis upon aging. Osteoarthritis and Cartilage. 2005;13:66–73
  79. Keystone EC. Abandoned therapies and unpublished trials in rheumatoid arthritis. Current Opinion in Rheumatology. 2003;15:253–258
  80. Berenbaum F. Signaling transduction: target in osteoarthritis. Current Opinion in Rheumatology. 2004;16:616–622
  81. Malemud CJ. Protein kinases in chondrocyte signaling and osteoarthritis. Clinical Orthopaedics and Related Research. 2004;427(supplement):S145–S151
  82. Fanning PJ, Emkey G, Smith RJ, et al. Mechanical regulation of mitogen-activated protein kinase signaling in articular cartilage. The Journal of Biological Chemistry. 2003;278:50940–50948
  83. Fitzgerald JB, Jin M, Dean D, et al. Mechanical compression of cartilage explants induces multiple time-dependent gene expression patterns and involves intracellular calcium and cyclic AMP. The Journal of Biological Chemistry. 2004;279:19502–19511
  84. Agarwal S, Deschner J, Long P, et al. Role of NF-kappaB transcription factors in antiinflammatory and proinflammatory actions of mechanical signals. Arthritis and Rheumatism. 2004;50:3541–3548
  85. Roshak AK, Callahan JF, Blake SM. Small-molecule inhibitors of NF-kappaB for the treatment of inflammatory joint disease. Current Opinion in Pharmacology. 2002;2:316–321
  86. Hammaker D, Sweeney S, Firestein GS. Signal transduction networks in rheumatoid arthritis. Annals of the Rheumatic Diseases. 2003;62(supplement 2):ii86–ii89
  87. McIntyre KW, Shuster DJ, Gillooly KM, et al. A highly selective inhibitor of I kappa B kinase, BMS-345541, blocks both joint inflammation and destruction in collagen-induced arthritis in mice. Arthritis and Rheumatism. 2003;48:2652–2659
  88. Pattoli MA, MacMaster JF, Gregor KR, et al. Collagen and aggrecan degradation is blocked in interleukin-1-treated cartilage explants by an inhibitor of IkappaB kinase through suppression of metalloproteinase expression. The Journal of Pharmacology and Experimental Therapeutics. 2005;315:382–388
  89. Pargellis C, Regan J. Inhibitors of p38 mitogen-activated protein kinase for the treatment of rheumatoid arthritis. Current Opinion in Investigational Drugs. 2003;4:566–571
  90. Badger AM, Blake S, Kapadia R, et al. Disease-modifying activity of SB 273005, an orally active, nonpeptide alphavbeta3 (vitronectin receptor) antagonist, in rat adjuvant-induced arthritis. Arthritis and Rheumatism. 2001;44:128–137
  91. Nishikawa M, Myoui A, Tomita T, et al. Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653. Arthritis and Rheumatism. 2003;48:2670–2681
  92. Zwerina J, Hayer S, Redlich K, et al. Activation of p38 MAPK is a key step in tumor necrosis factor-mediated inflammatory bone destruction. Arthritis and Rheumatism. 2006;54:463–472
  93. Dominguez C, Powers DA, Tamayo N. p38 MAP kinase inhibitors: many are made, but few are chosen. Current Opinion in Drug Discovery and Development. 2005;8:421–430
  94. Pramanik R, Qi X, Borowicz S, et al. p38 isoforms have opposite effects on AP-1-dependent transcription through regulation of c-Jun. The determinant roles of the isoforms in the p38 MAPK signal specificity. The Journal of Biological Chemistry. 2003;278:4831–4839
  95. Beier F. Cell-cycle control and the cartilage growth plate. Journal of Cellular Physiology. 2005;202:1–8
  96. Mavunkel BJ, Chakravarty S, Perumattam JJ, et al. Indole-based heterocyclic inhibitors of p38alpha MAP kinase: designing a conformationally restricted analogue. Bioorganic and Medicinal Chemistry Letters. 2003;13:3087–3090
  97. Wrobleski ST, Doweyko AM. Structural comparison of p38 inhibitor-protein complexes: a review of recent p38 inhibitors having unique binding interactions. Current Topics in Medicinal Chemistry. 2005;5:1005–1016
  98. Bogoyevitch MA, Boehm I, Oakley A, et al. Targeting the JNK MAPK cascade for inhibition: basic science and therapeutic potential. Biochimica et Biophysica Acta. 2004;1697:89–101
  99. Bogoyevitch MA. Therapeutic promise of JNK ATP-noncompetitive inhibitors. Trends in Molecular Medicine. 2005;11:232–239
  100. Bennett BL, Sasaki DT, Murray BW, et al. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proceedings of the National Academy of Sciences of the USA. 2001;98:13681–13686
  101. Clancy R, Rediske J, Koehne C, et al. Activation of stress-activated protein kinase in osteoarthritic cartilage: evidence for nitric oxide dependence. Osteoarthritis and Cartilage. 2001;9:294–299
  102. Loeser RF, Forsyth CB, Samarel AM, et al. Fibronectin fragment activation of proline-rich tyrosine kinase PYK2 mediates integrin signals regulating collagenase-3 expression by human chondrocytes through a protein kinase C-dependent pathway. The Journal of Biological Chemistry. 2003;278:24577–24585
  103. Ahmed S, Rahman A, Hasnain A, et al. Phenyl N-tert-butylnitrone down-regulates interleukin-1 beta-stimulated matrix metalloproteinase-13 gene expression in human chondrocytes: suppression of c-Jun NH2-terminal kinase, p38-mitogen-activated protein kinase and activating protein-1. The Journal of Pharmacology and Experimental Therapeutics. 2003;305:981–988
  104. Pelletier JP, Fernandes JC, Brunet J, et al. In vivo selective inhibition of mitogen-activated protein kinase kinase 1/2 in rabbit experimental osteoarthritis is associated with a reduction in the development of structural changes. Arthritis and Rheumatism. 2003;48:1582–1593
  105. Cha HS, Boyle DL, Inoue T, et al. The novel Syk inhibitor R406 blocks JNK-mediated gene expression in synoviocytes. The Journal of Pharmacology and Experimental Therapeutics. 2006;
  106. Hunziker EB. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis and Cartilage. 2002;10:432–463
  107. Brittberg M, Lindahl A, Nilsson A, et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. The New England Journal of Medicine. 1994;331:889–895
  108. Knutsen G, Engebretsen L, Ludvigsen TC, et al. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. The Journal of Bone and Joint Surgery. American Volume. 2004;86-A:455–464
  109. Lories RJ, Luyten FP. Bone morphogenetic protein signaling in joint homeostasis and disease. Cytokine and Growth Factor Reviews. 2005;16:287–298
  110. Seeherman H, Wozney JM. Delivery of bone morphogenetic proteins for orthopedic tissue regeneration. Cytokine and Growth Factor Reviews. 2005;16:329–345
  111. Sellers RS, Zhang R, Glasson SS, et al. Repair of articular cartilage defects one year after treatment with recombinant human bone morphogenetic protein-2 (rhBMP-2). The Journal of Bone and Joint Surgery. American Volume. 2000;82:151–160
  112. Louwerse RT, Heyligers IC, Klein-Nulend J, et al. Use of recombinant human osteogenic protein-1 for the repair of subchondral defects in articular cartilage in goats. Journal of Biomedical Materials Research. 2000;49:506–516
  113. Jelic M, Pecina M, Haspl M, et al. Regeneration of articular cartilage chondral defects by osteogenic protein-1 (bone morphogenetic protein-7) in sheep. Growth Factors. 2001;19:101–113
  114. Katayama R, Wakitani S, Tsumaki N, et al. Repair of articular cartilage defects in rabbits using CDMP1 gene-transfected autologous mesenchymal cells derived from bone marrow. Rheumatology (Oxford). 2004;43:980–985
  115. Gooch KJ, Blunk T, Courter DL, et al. Bone morphogenetic proteins-2, -12, and -13 modulate in vitro development of engineered cartilage. Tissue Engineering. 2002;8:591–601
  116. Hills RL, Belanger LM, Morris EA. Bone morphogenetic protein 9 is a potent anabolic factor for juvenile bovine cartilage, but not adult cartilage. Journal of Orthopaedic Research. 2005;23:611–617
  117. Tcacencu I, Carlsoo B, Stierna P. Effect of recombinant human BMP-2 on the repair of cricoid cartilage defects in young and adult rabbits: a comparative study. International Journal of Pediatric Otorhinolaryngology. 2005;69:1239–1246
  118. Zoricic S, Maric I, Bobinac D, et al. Expression of bone morphogenetic proteins and cartilage-derived morphogenetic proteins during osteophyte formation in humans. Journal of Anatomy. 2003;202:269–277
  119. Hunziker EB, Driesang IM, Morris EA. Chondrogenesis in cartilage repair is induced by members of the transforming growth factor-beta superfamily. Clinical Orthopaedics and Related Research. 2001;391(supplement):S171–S181
  120. Scharstuhl A, Glansbeek HL, van Beuningen HM, et al. Inhibition of endogenous TGF-beta during experimental osteoarthritis prevents osteophyte formation and impairs cartilage repair. The Journal of Immunology. 2002;169:507–514
  121. Scharstuhl A, Vitters EL, van der Kraan PM, et al. Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor beta/bone morphogenetic protein inhibitors during experimental osteoarthritis. Arthritis and Rheumatism. 2003;48:3442–3451
  122. Friedenstein AJ, Piatetzky S, Petrakova KV. Osteogenesis in transplants of bone marrow cells. Journal of Embryology and Experimental Morphology. 1966;16:381–390
  123. Tuan RS. Biology of developmental and regenerative skeletogenesis. Clinical Orthopaedics and Related Research. 2004;427(supplement):S105–S117
  124. Barry FP, Murphy JM. Mesenchymal stem cells: clinical applications and biological characterization. International Journal of Biochemistry and Cell Biology. 2004;36:568–584
  125. Caplan AI. Review: mesenchymal stem cells: cell-based reconstructive therapy in orthopedics. Tissue Engineering. 2005;11:1198–1211
  126. Magne D, Vinatier C, Julien M, et al. Mesenchymal stem cell therapy to rebuild cartilage. Trends in Molecular Medicine. 2005;11:519–526
  127. Urist MR. Bone: formation by autoinduction. Science. 1965;150:893–899
  128. Huang JI, Kazmi N, Durbhakula MM, et al. Chondrogenic potential of progenitor cells derived from human bone marrow and adipose tissue: a patient-matched comparison. Journal of Orthopaedic Research. 2005;23(6):1383–1389
  129. Palmer GD, Steinert A, Pascher A, et al. Gene-induced chondrogenesis of primary mesenchymal stem cells in vitro. Molecular Therapy. 2005;12:219–228
  130. Ikeda T, Kamekura S, Mabuchi A, et al. The combination of SOX5, SOX6, and SOX9 (the SOX trio) provides signals sufficient for induction of permanent cartilage. Arthritis and Rheumatism. 2004;50:3561–3573
  131. Tew SR, Li Y, Pothacharoen P, et al. Retroviral transduction with SOX9 enhances re-expression of the chondrocyte phenotype in passaged osteoarthritic human articular chondrocytes. Osteoarthritis and Cartilage. 2005;13:80–89
  132. Goldring MB. Are bone morphogenetic proteins effective inducers of cartilage repair? Ex vivo transduction of muscle-derived stem cells. Arthritis and Rheumatism. 2006;54:387–389
  133. Kuroda R, Usas A, Kubo S, et al. Cartilage repair using bone morphogenetic protein 4 and muscle-derived stem cells. Arthritis and Rheumatism. 2006;54:433–442
  134. El Hajjaji H, Williams JM, Devogelaer JP, et al. Treatment with calcitonin prevents the net loss of collagen, hyaluronan and proteoglycan aggregates from cartilage in the early stages of canine experimental osteoarthritis. Osteoarthritis and Cartilage. 2004;12:904–911
  135. Bagger YZ, Tanko LB, Alexandersen P, et al. Oral salmon calcitonin induced suppression of urinary collagen type II degradation in postmenopausal women: a new potential treatment of osteoarthritis. Bone. 2005;37:425–430
  136. Spector TD. Bisphosphonates: potential therapeutic agents for disease modification in osteoarthritis. Aging Clinical and Experimental Research. 2003;15:413–418
  137. Ham KD, Carlson CS. Effects of estrogen replacement therapy on bone turnover in subchondral bone and epiphyseal metaphyseal cancellous bone of ovariectomized cynomolgus monkeys. Journal of Bone and Mineral Research. 2004;19:823–829
  138. Radin EL, Rose RM. Role of subchondral bone in the initiation and progression of cartilage damage. Clinical Orthopaedics and Related Research. 1986;213:34–40
  139. Burr DB. Anatomy and physiology of the mineralized tissues: role in the pathogenesis of osteoarthrosis. Osteoarthritis and Cartilage. 2004;12(supplement A):S20–S30
  140. Buckland-Wright C. Subchondral bone changes in hand and knee osteoarthritis detected by radiography. Osteoarthritis and Cartilage. 2004;12(supplement A):S10–S19
  141. Mrosek EH, Lahm A, Erggelet C, et al. Subchondral bone trauma causes cartilage matrix degeneration: an immunohistochemical analysis in a canine model. Osteoarthritis and Cartilage. 2006;14:171–178
  142. Bailey AJ, Mansell JP, Sims TJ, et al. Biochemical and mechanical properties of subchondral bone in osteoarthritis. Biorheology. 2004;41:349–358
  143. Wang X, Manner PA, Horner A, et al. Regulation of MMP-13 expression by RUNX2 and FGF2 in osteoarthritic cartilage. Osteoarthritis and Cartilage. 2004;12:963–973
  144. Komuro H, Olee T, Kuhn K, et al. The osteoprotegerin/receptor activator of nuclear factor kappaB/receptor activator of nuclear factor kappaB ligand system in cartilage. Arthritis and Rheumatism. 2001;44:2768–2776
  145. Kishimoto K, Kitazawa R, Kurosaka M, et al. Expression profile of genes related to osteoclastogenesis in mouse growth plate and articular cartilage. Histochemistry and Cell Biology. 2006;125(5):593–602
  146. Pettit AR, Ji H, von Stechow D, et al. TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. American Journal of Pathology. 2001;159:1689–1699
  147. Loughlin J, Dowling B, Chapman K, et al. Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females. Proceedings of the National Academy of Sciences of the USA. 2004;101:9757–9762
  148. Lane NE, Lian K, Nevitt MC, et al. Frizzled related protein variants are risk factors for hip osteoarthritis. Arthritis and Rheumatism. 2006;54(4):1246–1254
  149. James IE, Kumar S, Barnes MR, et al. FrzB-2: a human secreted frizzled-related protein with a potential role in chondrocyte apoptosis. Osteoarthritis and Cartilage. 2000;8:452–463
  150. Tamamura Y, Otani T, Kanatani N, et al. Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification. The Journal of Biological Chemistry. 2005;280:19185–19195
  151. Ijiri K, Zerbini LF, Peng H, et al. A novel role for GADD45beta as a mediator of MMP-13 gene expression during chondrocyte terminal differentiation. The Journal of Biological Chemistry. 2005;280:38544–38555
  152. Guevremont M, Martel-Pelletier J, Massicotte F, et al. Human adult chondrocytes express hepatocyte growth factor (HGF) isoforms but not HgF: potential implication of osteoblasts on the presence of HGF in cartilage. Journal of Bone and Mineral Research. 2003;18:1073–1081
  153. Massicotte F, Fernandes JC, Martel-Pelletier J, et al. Modulation of insulin-like growth factor 1 levels in human osteoarthritic subchondral bone osteoblasts. Bone. 2006;38(3):333–341
  154. Haywood L, McWilliams DF, Pearson CI, et al. Inflammation and angiogenesis in osteoarthritis. Arthritis and Rheumatism. 2003;48:2173–2177
  155. Honorati MC, Neri S, Cattini L, Facchini A. Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts. Osteoarthritis and Cartilage. 2006;14(4):345–352
  156. Pufe T, Kurz B, Petersen W, et al. The influence of biomechanical parameters on the expression of VEGF and endostatin in the bone and joint system. Annals of Anatomy. 2005;187:461–472
  157. Pfander D, Cramer T, Swoboda B. Hypoxia and HIF-1alpha in osteoarthritis. International Orthopaedics. 2005;29:6–9
  158. François M, Richette P, Tsagris L, et al. Peroxisome proliferator-activated receptor-α-activation pathway potentiates interleukin-1 receptor antagonist production in cytokine-treated chondrocytes. Arthritis and Rheumatism. 2006;54(4):1233–1245
  159. Ling H, Recklies AD. The chitinase 3-like protein human cartilage glycoprotein 39 inhibits cellular responses to the inflammatory cytokines interleukin-1 and tumour necrosis factor-alpha. Biochemical Journal. 2004;380:651–659
  160. Recklies AD, Ling H, White C, Bernier SM. Inflammatory cytokines induce production of chitinase-3-like protein 1 by articular chondrocytes. The Journal of Biological Chemistry. 2005;280(50):41213–41221
  161. Yammani RR, Carlson CS, Bresnick AR et al. S100A4 activates receptor for advanced glycation end-products (RAGE) signaling and stimulates matrix metalloproteinase-13 production in human articular chondrocytes. Arthritis and Rheumatism [in press].
  162. Milner JE, Kevorkian L, Young DA, et al. Fibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritis. Arthritis Research and Therapy. 2006;8:R23
  163. Dumond H, Presle N, Terlain B, et al. Evidence for a key role of leptin in osteoarthritis. Arthritis and Rheumatism. 2003;48:3118–3129

PII: S1521-6942(06)00079-9

doi: 10.1016/j.berh.2006.06.003

Best Practice & Research Clinical Rheumatology
Volume 20, Issue 5 , Pages 1003-1025 , October 2006

Article Tools

* Image Usage & Resolution