Mechanical loading, cartilage degradation, and arthritis

Annals of the New York Academy of Sciences

Volumn 1211, Issue , 2010, Pages 37-50

  Sun, Hui B ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Arthritis; Cartilage degradation; Mechanical loading

Indexed keywords

ADAM PROTEIN; MATRIX METALLOPROTEINASE; TISSUE INHIBITOR OF METALLOPROTEINASE;

ANGIOGENESIS; ARTHRITIS; ARTICLE; CARTILAGE DEGENERATION; DISEASE ACTIVITY; EPIGENETICS; GENE CONTROL; HOMEOSTASIS; HUMAN; MECHANICAL STIMULATION; MECHANICAL STRESS; NONHUMAN; OSTEOARTHRITIS; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; WOUND HEALING;

EID: 78349291080     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1111/j.1749-6632.2010.05808.x     Document Type: Article

References (166)

1. Arendt, E. & R. Dick 1995. Knee injury patterns among men and women in collegiate basketball and soccer. NCAA data and review of literature. Am. J. Sports Med. 23: 694-701.
2. Jones, S.J., R.A. Lyons, J. Sibert, R. Evans, et al 2001. Changes in sports injuries to children between 1983 and 1998: comparison of case series. J. Public Health Med. 23: 268-271.
3. Levy, A.S., J. Lohnes, S. Sculley, M. LeCroy, et al 1996. Chondral delamination of the knee in soccer players. Am. J. Sports Med. 24: 634-639.
4. Mandelbaum, B.R. et al 1998. Articular cartilage lesions of the knee. Am. J. Sports Med. 26: 853-861.
5. Moti, A.W. & L.J. Micheli 2003. Meniscal and articular cartilage injury in the skeletally immature knee. Instr. Course Lect. 52: 683-690.
6. Smith, A.D. & S.S. Tao 1995. Knee injuries in young athletes. Clin. Sports Med. 14: 629-650.
7. Piasecki, D.P., K.P. Spindler, T.A. Warren, et al 2003. Intraarticular injuries associated with anterior cruciate ligament tear: findings at ligament reconstruction in high school and recreational athletes. An analysis of sex-based differences. Am. J. Sports Med. 31: 601-605.
8. Buckwalter, J.A. & J.A. Martin 2006. Osteoarthritis. Adv. Drug Deliv. Rev. 58: 150-167.
9. Saxon, L., C. Finch & S. Bass 1999. Sports participation, sports injuries and osteoarthritis: implications for prevention. Sports Med. 28: 123-135.
10. Torzilli, P.A., R. Grigiene, J. Borrelli Jr. & D.L. Helfet 1999. Effect of impact load on articular cartilage: cell metabolism and viability, and matrix water content. J. Biomech. Eng. 121: 433-441.
11. Loening, A.M. et al 2000. Injurious mechanical compression of bovine articular cartilage induces chondrocyte apoptosis. Arch. Biochem. Biophys. 381: 205-212.
12. Kurz, B. et al 2001. Biosynthetic response and mechanical properties of articular cartilage after injurious compression. J. Orthop. Res. 19: 1140-1146.
13. Morel, V. & T.M. Quinn 2004. Cartilage injury by ramp compression near the gel diffusion rate. J. Orthop. Res. 22: 145-151.
14. Chen, C.T., N. Burton-Wurster, G. Lust, R.A. Bank, et al 1999. J.M. Compositional and metabolic changes in damaged cartilage are peak-stress, stress-rate, and loading-duration dependent. J. Orthop. Res. 17: 870-879.
15. Chen, C.T. et al 2001.Chondrocyte necrosis and apoptosis in impact damaged articular cartilage. J. Orthop. Res. 19: 703-711.
16. Jones, M.H. & A.S. Amendola 2007. Acute treatment of inversion ankle sprains: immobilization versus functional treatment. Clin. Orthop. Relat. Res. 455: 169-172.
17. McCarthy, C. & E. Oakley 2002. Management of suspected cervical spine injuries: the paediatric perspective. Accid. Emerg. Nurs. 10: 163-169.
18. Fontaine, K.R., M. Heo & J. Bathon 2004. Are US adults with arthritis meeting public health recommendations for physical activity? Arthritis Rheum. 50: 624-628.
19. Haapala, J. et al 1999. Remobilization does not fully restore immobilization induced articular cartilage atrophy. Clin. Orthop. Relat. Res. 362: 218-229.
20. Jurvelin, J., I. Kiviranta, M. Tammi & J.H. Helminen 1986. Softening of canine articular cartilage after immobilization of the knee joint. Clin Orthop. Relat. Res. 207: 246-252.
21. Haapala, J. et al 2000. Incomplete restoration of immobilization induced softening of young beagle knee articular cartilage after 50-week remobilization. Int. J. Sports Med. 21: 76-81.
22. Haapala, J. et al 1996. Coordinated regulation of hyaluronan and aggrecan content in the articular cartilage of immobilized and exercised dogs. J. Rheumatol. 23: 1586-1593.
23. Evans, E.B., G.W.N. Eggers, J.K. Butler & J. Blumel 1960. Experimental immobilization and remobilization of rat knee joints. J. Bone Joint Surg. Am. 42: 737-758.
24. Hagiwara, Y. et al 2009. Changes of articular cartilage after immobilization in a rat knee contracture model. J. Orthop. Res. 27: 236-242.
25. Vanwanseele, B., F. Eckstein, H. Knecht, A. Spaepen 2003. Longitudinal analysis of cartilage atrophy in the knees of patients with spinal cord injury. Arthritis Rheum. 48: 3377-3381.
26. Hinterwimmer, S. et al 2004. Cartilage atrophy in the knees of patients after seven weeks of partial load bearing. Arthritis Rheum. 50: 2516-2520.
27. Buckwalter, J.A. & H.J. Mankin 1998. Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr. Course Lect. 47: 487-504.
28. Jackson, D.W., P.A. Lalor, H.M. Aberman & T.M. Simon 2001. Spontaneous repair of full-thickness defects of articular cartilage in a goat model. A preliminary study. J. Bone Joint Surg. Am. 83-A, 53-64.
29. Vrahas, M.S., K. Mithoefer & D. Joseph 2004. The long-term effects of articular impaction. Clin. Orthop. Relat. Res. 423: 40-43.
30. Lohmander, L.S., H. Roos, L. Dahlberg, L.A. Hoerrner, et al 1994. M.W. Temporal patterns of stromelysin-1, tissue inhibitor, and proteoglycan fragments in human knee joint fluid after injury to the cruciate ligament or meniscus. J. Orthop. Res. 12: 21-28.
31. Peat, G., P. Croft & E. Hay 2001. Clinical assessment of the osteoarthritis patient. Best Pract. Res. Clin. Rheumatol. 15: 527-544.
32. Sinkov, V. & T. Cymet 2003. Osteoarthritis: understanding the pathophysiology, genetics, and treatments. J. Natl. Med. Assoc. 95: 475-482.
33. Hinton, R., R.L. Moody, A.W. Davis & S.F. Thomas 2002. Osteoarthritis: diagnosis and therapeutic considerations. Am. Fam. Physician. 65: 841-848.
34. Felson, D.T. et al 2000. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann. Intern. Med. 133: 635-646.
35. Benito, M.J., D.J. Veale, O. FitzGerald & W.B. Van Den Berg 2005. Synovial tissue inflammation in early and late osteoarthritis. Ann. Rheum. Dis. 64: 1263-1267.
36. Abramson, S.B. & M. Attur 2009. Developments in the scientific understanding of osteoarthritis. Arthritis Res. Ther. 11: 227.
37. Derfus, B.A. et al 2002. The high prevalence of pathologic calcium crystals in pre-operative knees. J. Rheumatol. 29: 570-574.
38. Myers, S.L., D. Flusser, K.D. Brandt & D.A. Heck 1992. Prevalence of cartilage shards in synovium and their association with synovitis in patients with early and endstage osteoarthritis. J. Rheumatol. 19: 1247-1251.
39. Sutton, S. et al 2009. The contribution of the synovium, synovial derived inflammatory cytokines and neuropeptides to the pathogenesis of osteoarthritis. Vet. J. 179: 10-24.
40. Rollin, R. et al 2008. Early lymphocyte activation in the synovial microenvironment in patients with osteoarthritis: comparison with rheumatoid arthritis patients and healthy controls. Rheumatol. Int. 28: 757-764.
41. Da, R.R., Y. Qin, D. Baeten & Y. Zhang 2007. B cell clonal expansion and somatic hypermutation of Ig variable heavy chain genes in the synovial membrane of patients with osteoarthritis. J. Immunol. 178: 557-565.
42. Attur, M., J. Samuels, S. Krasnokutsky & S.B. Abramson 2010. Targeting the synovial tissue for treating osteoarthritis (OA): where is the evidence? Best Pract. Res. Clin. Rheumatol. 24: 71-79.
43. Abdel-Nasser, A.M., J.J. Rasker & H.A. Valkenburg 1997. Epidemiological and clinical aspects relating to the variability of rheumatoid arthritis. Semin. Arthritis Rheum. 27: 123-140.
44. Yelin, E., R. Meenan, M. Nevitt & W. Epstein 1980. Work disability in rheumatoid arthritis: effects of disease, social, and work factors. Ann. Intern. Med. 93: 551-556.
45. Kobelt, G., K. Eberhardt, L. Jonsson & B. Jonsson 1999. Economic consequences of the progression of rheumatoid arthritis in Sweden. Arthritis Rheum. 42: 347-356.
46. Arend, W.P. 2001. Cytokine imbalance in the pathogenesis of rheumatoid arthritis: the role of interleukin-1 receptor antagonist. Semin. Arthritis Rheum. 30: 1-6.
47. Brennan, F.M. & I.B. McInnes 2008. Evidence that cytokines play a role in rheumatoid arthritis. J. Clin. Invest. 118: 3537-3545.
48. Tran, C.N., S.K. Lundy & D.A. Fox 2005. Synovial biology and T cells in rheumatoid arthritis. Pathophysiology. 12: 183-189.
49. Ferrara, N., H.P. Gerber & J. LeCouter 2003. The biology of VEGF and its receptors. Nat. Med. 9: 669-676.
50. Koch, A.E. 1998. Review: angiogenesis: implications for rheumatoid arthritis. Arthritis Rheum. 41: 951-962.
51. Yoo, S.A., S.K. Kwok & W.U. Kim 2008. Proinflammatory role of vascular endothelial growth factor in the pathogenesis of rheumatoid arthritis: prospects for therapeutic intervention. Mediators Inflamm. 2008: 129873.
52. Lee, S.S. et al 2001. Vascular endothelial growth factor levels in the serum and synovial fluid of patients with rheumatoid arthritis. Clin. Exp. Rheumatol. 19: 321-324.
53. Mould, A.W. et al 2003. Vegfb gene knockout mice display reduced pathology and synovial angiogenesis in both antigen-induced and collagen-induced models of arthritis. Arthritis Rheum. 48: 2660-2669.
54. Goldring, M.B. & K.B. Marcu 2009. Cartilage homeostasis in health and rheumatic diseases. Arthritis Res. Ther. 11: 224-240.
55. Aigner, T. & L. McKenna 2002. Molecular pathology and pathobiology of osteoarthritic cartilage. Cell Mol. Life Sci. 59: 5-18.
56. Cawston, T.E. & A.J. Wilson 2006. Understanding the role of tissue degrading enzymes and their inhibitors in development and disease. Best Pract. Res. Clin. Rheumatol. 20: 983-1002.
57. Rengel, Y., C. Ospelt & S. Gay 2007. Proteinases in the joint: clinical relevance of proteinases in joint destruction. Arthritis Res. Ther. 9: 221-230.
58. Burrage, P.S., K.S. Mix & C.E. Brinckerhoff 2006. Matrix metalloproteinases: role in arthritis. Front. Biosci. 11: 529-543.
59. Tortorella, M.D. et al 1999. Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins. Science 284: 1664-1666.
60. Gendron, C. et al 2007. Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4. J. Biol. Chem. 282: 18294-18306.
61. Porter, S., I.M. Clark, L. Kevorkian & D.R. Edwards 2005. The ADAMTS metalloproteinases. Biochem. J. 386: 15-27.
62. Black, R.A. et al 1997. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature 385: 729-733.
63. Moss, M.L. et al 1997. Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature 385: 733-736.
64. Crowe, P.D. et al 1995. A metalloprotease inhibitor blocks shedding of the 80-kD TNF receptor and TNF processing in T lymphocytes. J. Exp. Med. 181: 1205-1210.
65. White, J.M. 2003. ADAMs: modulators of cell-cell and cell-matrix interactions. Curr. Opin. Cell Biol. 15: 598-606.
66. Brew, K. & H. Nagase 2010. The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity. Biochim. Biophys. Acta. 1803: 55-71.
67. Hamze, A.B. et al 2007. Constraining specificity in the N-domain of tissue inhibitor of metalloproteinases-1: gelatinase-selective inhibitors. Protein Sci. 16: 1905-1913.
68. Nagase, H. & G. Murphy 2008. Tailoring TIMPs for selective metalloproteinase inhibition. Springer Science. New York
69. Amour, A. et al 2000. The in vitro activity of ADAM-10 is inhibited by TIMP-1 and TIMP-3. FEBS Lett. 473: 275-279.
70. Amour, A. et al 1998. TNF-alpha converting enzyme (TACE) is inhibited by TIMP-3. FEBS Lett. 435: 39-44.
71. Kashiwagi, M., M. Tortorella, H. Nagase & K. Brew 2001. TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4) and aggrecanase 2 (ADAM-TS5). J. Biol. Chem. 276: 12501-12504.
72. Wang, W.M., G. Ge, N.H. Lim, et al 2006. TIMP-3 inhibits the procollagen N-proteinase ADAMTS-2. Biochem. J. 398: 515-519.
73. Sahebjam, S., R. Khokha & J.S. Mort 2007. Increased collagen and aggrecan degradation with age in the joints of Timp3(-/-) mice. Arthritis Rheum. 56: 905-909.
74. Fanjul-Fernandez, M., A.R. Folgueras, S. Cabrera & C. Lopez-Otin 2010. Matrix metalloproteinases: evolution, gene regulation and functional analysis in mouse models. Biochim. Biophys. Acta. 1803: 3-19.
75. McQuibban, G.A. et al 2002. Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo. Blood 100: 1160-1167.
76. Nagase, H., R. Visse & G. Murphy 2006. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc. Res. 69: 562-573.
77. Itoh, T. et al 2002. The role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in antibody-induced arthritis. J. Immunol. 169: 2643-2647.
78. Clements, K.M. et al 2003. Gene deletion of either interleukin-1beta, interleukin-1beta-converting enzyme, inducible nitric oxide synthase, or stromelysin 1 accelerates the development of knee osteoarthritis in mice after surgical transection of the medial collateral ligament and partial medial meniscectomy. Arthritis Rheum. 48: 3452-3463.
79. Holmbeck, K. et al 1999. MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 99: 81-92.
80. Bohm, B.B. et al 2005. Homeostatic effects of the metalloproteinase disintegrin ADAM15 in degenerative cartilage remodeling. Arthritis Rheum. 52: 1100-1109.
81. Ferretti, M. et al 2006. Biomechanical signals suppress proinflammatory responses in cartilage: early events in experimental antigen-induced arthritis. J. Immunol. 177: 8757-8766.
82. Ferretti, M. et al 2005. Anti-inflammatory effects of continuous passive motion on meniscal fibrocartilage. J Orthop Res. 23: 1165-1171.
83. Salter, R.B. 2004. Continuous passive motion: from origination to research to clinical applications. J. Rheumatol. 31: 2104-2105.
84. Ikenoue, T. et al 2003. Mechanoregulation of human articular chondrocyte aggrecan and type II collagen expression by intermittent hydrostatic pressure in vitro. J. Orthop. Res. 21: 110-116.
85. Lee, D.A. & D.L. Bader 1997. Compressive strains at physiological frequencies influence the metabolism of chondrocytes seeded in agarose. J. Orthop. Res. 15: 181-188.
86. Shelton, J.C., D.L. Bader & D.A. Lee 2003. Mechanical conditioning influences the metabolic response of cell-seeded constructs. Cells Tissues Organs 175: 140-150.
87. Mauck, R.L. et al 2000. Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels. J. Biomech. Eng. 122: 252-260.
88. Sharma, G., R.K. Saxena & P. Mishra 2007. Differential effects of cyclic and static pressure on biochemical and morphological properties of chondrocytes from articular cartilage. Clin Biomech (Bristol, Avon). 22: 248-255.
89. Millward-Sadler, S.J., M.O. Wright, L.W. Davies, et al 2000. Mechanotransduction via integrins and interleukin-4 results in altered aggrecan and matrix metalloproteinase 3 gene expression in normal, but not osteoarthritic, human articular chondrocytes. Arthritis Rheum. 43: 2091-2099.
90. Kamiya, T. et al 2010. Effects of mechanical stimuli on the synthesis of superficial zone protein in chondrocytes. J. Biomed. Mater. Res. A. 92: 801-805.
91. Parkkinen, J.J., M.J. Lammi, H.J. Helminen & M. Tammi 1992. Local stimulation of proteoglycan synthesis in articular cartilage explants by dynamic compression in vitro. J. Orthop. Res. 10: 610-620.
92. Valhmu, W.B. et al 1998. Load-controlled compression of articular cartilage induces a transient stimulation of aggrecan gene expression. Arch. Biochem. Biophys. 353: 29-36.
93. Otterness, I.G. et al 1998. Exercise protects against articular cartilage degeneration in the hamster. Arthritis Rheum. 41: 2068-2076.
94. Galois, L. et al 2003. Moderate-impact exercise is associated with decreased severity of experimental osteoarthritis in rats. Rheumatology (Oxford) 42: 692-693. author reply 693-694.
95. Manninen, P., H. Riihimaki, M. Heliovaara & O. Suomalainen 2001. Physical exercise and risk of severe knee osteoarthritis requiring arthroplasty. Rheumatology (Oxford) 40: 432-437.
96. Roos, E.M. & L. Dahlberg 2005. Positive effects of moderate exercise on glycosaminoglycan content in knee cartilage: a four-month, randomized, controlled trial in patients at risk of osteoarthritis. Arthritis Rheum. 52: 3507-3514.
97. Miller, G.D. et al 2003. The Arthritis, Diet and Activity Promotion Trial (ADAPT): design, rationale, and baseline results. Control Clin. Trials 24: 462-480.
98. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. 2000. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum. 43: 1905-1915.
99. Jordan, K.M. et al 2003. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann. Rheum. Dis. 62: 1145-1155.
100. Ettinger, W.H. Jr., et al 1997. A randomized trial comparing aerobic exercise and resistance exercise with a health education program in older adults with knee osteoarthritis. The Fitness Arthritis and Seniors Trial (FAST). JAMA. 277: 25-31.
101. O'Reilly, S.C., K.R. Muir & M. Doherty 1999. Effectiveness of home exercise on pain and disability from osteoarthritis of the knee: a randomised controlled trial. Ann. Rheum. Dis. 58: 15-19.
102. Van Baar, M.E. et al 1998. The effectiveness of exercise therapy in patients with osteoarthritis of the hip or knee: a randomized clinical trial. J. Rheumatol. 25: 2432-2439.
103. Ekblom, B., O. Lovgren, M. Alderin, et al 1975. Effect of short-term physical training on patients with rheumatoid arthritis. a six-month follow-up study. Scand. J. Rheumatol. 4: 87-91.
104. Stenstrom, C.H. & M.A. Minor 2003. Evidence for the benefit of aerobic and strengthening exercise in rheumatoid arthritis. Arthritis Rheum. 49: 428-434.
105. Sambajon, V.V., J.E. Cillo Jr., R.J. Gassner & M.J. Buckley 2003. The effects of mechanical strain on synovial fibroblasts. J. Oral Maxillofac. Surg. 61: 707-712.
106. Sun, H.B., R. Nalim & H. Yokota 2003. Expression and activities of matrix metalloproteinases under oscillatory shear in IL-1-stimulated synovial cells. Connect Tissue Res. 44: 42-49.
107. Sun, H.B. & H. Yokota 2002. Reduction of cytokine-induced expression and activity of MMP-1 and MMP-13 by mechanical strain in MH7A rheumatoid synovial cells. Matrix Biol. 21: 263-270.
108. Torzilli, P.A., M. Bhargava, S. Park & C.T. Chen 2010. Mechanical load inhibits IL-1 induced matrix degradation in articular cartilage. Osteoarthritis Cartilage. 1: 97-105.
109. Heckman, J.D., J.P. Ryaby, J. McCabe, et al 1994. Acceleration of tibial fracture-healing by non-invasive, low-intensity pulsed ultrasound. J. Bone Joint Surg. Am. 76: 26-34.
110. Kristiansen, T.K., J.P. Ryaby, J. McCabe, et al 1997. Accelerated healing of distal radial fractures with the use of specific, low-intensity ultrasound. A multicenter, prospective, randomized, double-blind, placebo-controlled study. J. Bone Joint Surg. Am. 79: 961-973.
111. Watanabe, Y., T. Matsushita, M. Bhandari, et al 2010. Ultrasound for fracture healing: current evidence. J. Orthop. Trauma 24(Suppl. 1): S56-S61.
112. Mukai, S. et al 2005. Transforming growth factor-beta1 mediates the effects of low-intensity pulsed ultrasound in chondrocytes. Ultrasound Med. Biol. 31: 1713-1721.
113. Naito, K. et al 2010. Low-intensity pulsed ultrasound (LIPUS) increases the articular cartilage type II collagen in a rat osteoarthritis model. J. Orthop. Res. 28: 361-369.
114. Rutjes, A.W., E. Nuesch, R. Sterchi & P. Juni 2010. Therapeutic ultrasound for osteoarthritis of the knee or hip. Cochrane Database Syst. Rev. CD003132.
115. Lee, J.H., J.B. Fitzgerald, M.A. Dimicco & A.J. Grodzinsky 2005. Mechanical injury of cartilage explants causes specific time-dependent changes in chondrocyte gene expression. Arthritis Rheum. 52: 2386-2395.
116. Blain, E.J. 2007. Mechanical regulation of matrix metalloproteinases. Front. Biosci. 12: 507-527.
117. Wong, M. & D.R. Carter 2003. Articular cartilage functional histomorphology and mechanobiology: a research perspective. Bone 33: 1-13.
118. Fitzgerald, J.B. et al 2008. Shear- and compression-induced chondrocyte transcription requires MAPK activation in cartilage explants. J. Biol. Chem. 283: 6735-6743.
119. Agarwal, S. et al 2004. Role of NF-kappaB transcription factors in antiinflammatory and proinflammatory actions of mechanical signals. Arthritis Rheum. 50: 3541-3548.
120. Pulai, J.I. et al 2005. NF-kappa B mediates the stimulation of cytokine and chemokine expression by human articular chondrocytes in response to fibronectin fragments. J. Immunol. 174: 5781-5788.
121. Pufe, T. et al 2004. Vascular endothelial growth factor (VEGF) induces matrix metalloproteinase expression in immortalized chondrocytes. J. Pathol. 202: 367-374.
122. Kurz, B. et al 2005. Pathomechanisms of cartilage destruction by mechanical injury. Ann. Anat. 187: 473-485.
123. Amin, A.R. et al 1997. Superinduction of cyclooxygenase-2 activity in human osteoarthritis-affected cartilage. Influence of nitric oxide. J. Clin. Invest. 99: 1231-1237.
124. Kang, R.Y., J. Freire-Moar, E. Sigal & C.Q. Chu 1996. Expression of cyclooxygenase-2 in human and an animal model of rheumatoid arthritis. Br. J. Rheumatol. 35: 711-718.
125. Sano, H. et al 1992. In vivo cyclooxygenase expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis and rats with adjuvant and streptococcal cell wall arthritis. J. Clin. Invest. 89: 97-108.
126. Anderson, G.D. et al 1996. Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin 6 in rat adjuvant arthritis. J. Clin. Invest. 97: 2672-2679.
127. Portanova, J.P. et al 1996. Selective neutralization of prostaglandin E2 blocks inflammation, hyperalgesia, and interleukin 6 production in vivo. J. Exp. Med. 184: 883-891.
128. Healy, Z.R., F. Zhu, J.D. Stull & K. Konstantopoulos 2008. Elucidation of the signaling network of COX-2 induction in sheared chondrocytes: COX-2 is induced via a Rac/MEKK1/MKK7/JNK2/c-Jun-C/EBPbeta-dependent pathway. Am. J. Physiol. Cell Physiol. 294: C1146-C1157.
129. Hardy, M.M. et al 2002. Cyclooxygenase 2-dependent prostaglandin E2 modulates cartilage proteoglycan degradation in human osteoarthritis explants. Arthritis Rheum. 46: 1789-1803.
130. Laufer, S. 2003. Role of eicosanoids in structural degradation in osteoarthritis. Curr. Opin. Rheumatol. 15: 623-627.
131. Miwa, M. et al 2000. Induction of apoptosis in bovine articular chondrocyte by prostaglandin E(2) through cAMP-dependent pathway. Osteoarthritis Cartilage 8: 17-24.
132. Jacques, C. et al 1999. Cyclooxygenase activity in chondrocytes from osteoarthritic and healthy cartilage. Rev. Rhum. Engl. Ed. 66: 701-704.
133. McCoy, J.M., J.R. Wicks & L.P. Audoly 2002. The role of prostaglandin E2 receptors in the pathogenesis of rheumatoid arthritis. J. Clin. Invest. 110: 651-658.
134. Jeffrey, J.E. & R.M. Aspden 2007. Cyclooxygenase inhibition lowers prostaglandin E2 release from articular cartilage and reduces apoptosis but not proteoglycan degradation following an impact load in vitro. Arthritis Res. Ther. 9: R129-R139.
135. Chowdhury, T.T., D.M. Salter, D.L. Bader & D.A. Lee 2008. Signal transduction pathways involving p38 MAPK, JNK, NFkappaB and AP-1 influences the response of chondrocytes cultured in agarose constructs to IL-1beta and dynamic compression. Inflamm. Res. 57: 306-313.
136. Ando, A. et al 2009. Increased expression of metalloproteinase-8 and -13 on articular cartilage in a rat immobilized knee model. Tohoku J. Exp. Med. 217: 271-278.
137. Leong, D.J. et al 2010. Matrix metalloproteinase-3 in articular cartilage is upregulated by joint immobilization and suppressed by passive joint motion. Matrix Biol. 29: 420-426.
138. Vanwanseele, B., E. Lucchinetti & E. Stussi 2002. The effects of immobilization on the characteristics of articular cartilage: current concepts and future directions. Osteoarthritis Cartilage 10: 408-419.
139. Sakamoto, J. et al 2009. Immobilization-induced cartilage degeneration mediated through expression of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and chondromodulin-I. Connect Tissue Res. 50: 37-45.
140. Trudel, G., H.K. Uhthoff & O. Laneuville 2005. Prothrombin gene expression in articular cartilage with a putative role in cartilage degeneration secondary to joint immobility. J. Rheumatol. 32: 1547-1555.
141. Basso, N. & J.N. Heersche 2006. Effects of hind limb unloading and reloading on nitric oxide synthase expression and apoptosis of osteocytes and chondrocytes. Bone 39: 807-814.
142. Chowdhury, T.T., D.L. Bader & D.A. Lee 2006. Anti-inflammatory effects of IL-4 and dynamic compression in IL-1beta stimulated chondrocytes. Biochem. Biophys. Res. Commun. 339: 241-247.
143. Chowdhury, T.T., D.L. Bader & D.A. Lee 2003. Dynamic compression counteracts IL-1 beta-induced release of nitric oxide and PGE2 by superficial zone chondrocytes cultured in agarose constructs. Osteoarthritis Cartilage 11: 688-696.
144. Deschner, J., B. Rath-Deschner & S. Agarwal 2006. Regulation of matrix metalloproteinase expression by dynamic tensile strain in rat fibrochondrocytes. Osteoarthritis Cartilage 14: 264-272.
145. Yokota, H., M.B. Goldring & H.B. Sun 2003. CITED2-mediated regulation of MMP-1 and MMP-13 in human chondrocytes under flow shear. J. Biol. Chem. 278: 47275-47280.
146. Dittmer, J. 2003. The biology of the Ets1 proto-oncogene. Mol. Cancer 2: 29-50
147. Millward-Sadler, S.J. et al 1999. Integrin-regulated secretion of interleukin 4: a novel pathway of mechanotransduction in human articular chondrocytes. J. Cell Biol. 145: 183-189.
148. Wright, M.O. et al 1997. Hyperpolarisation of cultured human chondrocytes following cyclical pressure-induced strain: evidence of a role for alpha 5 beta 1 integrin as a chondrocyte mechanoreceptor. J. Orthop. Res. 15: 742-747.
149. Seguin, C.A. & S.M. Bernier 2003. TNFalpha suppresses link protein and type II collagen expression in chondrocytes: Role of MEK1/2 and NF-kappaB signaling pathways. J. Cell Physiol. 197: 356-369.
150. Ghosh, S. & M. Karin 2002. Missing pieces in the NF-kappaB puzzle. Cell 109 (Suppl.): S81-S96.
151. Hoffmann, A., A. Levchenko, M.L. Scott & D. Baltimore 2002. The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation. Science 298: 1241-1245.
152. Liacini, A. et al 2003. Induction of matrix metalloproteinase-13 gene expression by TNF-alpha is mediated by MAP kinases, AP-1, and NF-kappaB transcription factors in articular chondrocytes. Exp. Cell. Res. 288: 208-217.
153. Madhavan, S. et al 2007. Biomechanical signals suppress TAK1 activation to inhibit NF-kappaB transcriptional activation in fibrochondrocytes. J. Immunol. 179: 6246-6254.
154. Dossumbekova, A. et al 2007. Biomechanical signals inhibit IKK activity to attenuate NF-kappaB transcription activity in inflamed chondrocytes. Arthritis Rheum. 56: 3284-3296.
155. Bird, A. 2002. DNA methylation patterns and epigenetic memory. Genes Dev. 16: 6-21.
156. Reik, W. 2007. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447: 425-432.
157. Feinberg, A.P. 2007. Phenotypic plasticity and the epigenetics of human disease. Nature 447: 433-440.
158. Cheung, K.S., K. Hashimoto, N. Yamada & H.I. Roach 2009. Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation. Rheumatol. Int. 29: 525-534.
159. H.I. Roach, et al 2005. Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions. Arthritis Rheum. 52: 3110-3124.
160. Iliopoulos, D., K.N. Malizos & A. Tsezou 2007. Epigenetic regulation of leptin affects MMP-13 expression in osteoarthritic chondrocytes: possible molecular target for osteoarthritis therapeutic intervention. Ann. Rheum. Dis. 66: 1616-1621.
161. Loeser, R.F., H.J. Im, B. Richardson, et al 2009. Methylation of the OP-1 promoter: potential role in the age-related decline in OP-1 expression in cartilage. Osteoarthritis Cartilage 17: 513-517.
162. Kouzarides, T. 2000. Acetylation: a regulatory modification to rival phosphorylation? EMBO J. 19: 1176-1179.
163. Young, D.A. et al 2005. Histone deacetylase inhibitors modulate metalloproteinase gene expression in chondrocytes and block cartilage resorption. Arthritis Res. Ther. 7: R503-R512.
164. Chung, Y.L., M.Y. Lee, A.J. Wang & L.F. Yao 2003. A therapeutic strategy uses histone deacetylase inhibitors to modulate the expression of genes involved in the pathogenesis of rheumatoid arthritis. Mol. Ther. 8: 707-717.
165. Illi, B. et al 2003. Shear stress-mediated chromatin remodeling provides molecular basis for flow-dependent regulation of gene expression. Circ. Res. 93: 155-161.
166. Illi, B. et al 2005. Epigenetic histone modification and cardiovascular lineage programming in mouse embryonic stem cells exposed to laminar shear stress. Circ. Res. 96: 501-508.