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Integrin-Dependent Signal Cascades in Chondrocyte Mechanotransduction

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Abstract

Mechanical forces influence chondrocyte metabolism and are critically important for maintenance of normal cartilage structure and integrity. In cells of the musculoskeletal system and mechanoresponsive cells in other tissues, integrins seem to be involved in the mechanotransduction process. Integrin activity is important in the early cellular responses to mechanical stimulation, regulating activation of a number of intracellular cascades that induce changes in gene expression and tissue remodeling. In normal human articular chondrocytes, integrin activation, consequent to mechanical stimulation in vitro, results in tyrosine phosphorylation of regulatory proteins and subsequent secretion of autocrine and paracrine acting soluble mediators including substance P and interleukin 4. Significant differences in signaling events and cellular responses are seen when normal and osteoarthritic chondrocytes are mechanically stimulated. These differences may relate to differences in integrin expression and function. Improved comprehension of how integrins mediate chondrocyte responses to mechanical stimulation, and how cross talk between integrin signaling, extracellular matrix, and autocrine/paracrine signaling molecules regulate mechanotransduction and cellular reactions are necessary for further understanding of how load influences cartilage structure.

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REFERENCES

  1. Aplin, A. E., A. Howe, S. K. Alahari, and R. L. Juliano. Signal transduction and signal modulation by cell adhesion receptors: the role of integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins. Pharmacol. Rev. 50:197-263, 1998.

    Google Scholar 

  2. Arner, E. C., and M. A. Pratta. Modulation of interleukin-1-induced alterations in cartilage proteoglycan metabolism by activation of protein kinase C. Arthritis Rheum. 34:1006-1013, 1991.

    Google Scholar 

  3. Arner, E. C., and M. C. Tortorella. Signal transduction through chondrocyte integrin receptors induces matrix metalloproteinase synthesis and synergises with interleukin-1. Arthritis Rheum. 38:1304-1314, 1995.

    Google Scholar 

  4. Attur, M. G., M. N. Dave, R. M. Clancy, I. R. Patel, S. B. Abramson, and A. R. Amin. Functional genomic analysis in arthritis-affected cartilage: Yin-yang regulation of inflammatory mediators by a5β1 and aVβ3 integrins. J. Immunol. 164:2684-2691, 2000.

    Google Scholar 

  5. Bjelle, A. O. Content and composition of glycosaminoglycans in human knee joint cartilage. Variation with site and age in adults. Connect. Tissue. Res. 3:141-147, 1975.

    Google Scholar 

  6. Bonassar, L. J., A. J. Grodzinsky, E. H. Frank, S. G. Davila, N. R. Bhaktav, and S. B. Trippel. The effect of dynamic compression on the response of articular cartilage to insulin-like growth factor-I. J. Orthop. Res. 19:11-17, 2001.

    Google Scholar 

  7. Bonassar, L. J., J. D. Sandy, M. W. Lark, A. H. Plaas, E. H. Frank, and A. J. Grodzinsky. Inhibition of cartilage degradation and changes in physical properties induced by IL-1beta and retinoic acid using matrix metalloproteinase inhibitors. Arch. Biochem. Biophys. 344:404-412, 1997.

    Google Scholar 

  8. Brandt, K. D., S. L. Myers, D. Burr, and M. Albrecht. Osteoarthritic changes in canine articular cartilage, subchondral bone, and synovium fifty-four months after transection of the anterior cruciate ligament. Arthritis Rheum. 34:1560-1570, 1991.

    Google Scholar 

  9. Buschmann, M. D., Y. J. Kim, M. Wong, E. Frank, E. B. Hunziker, and A. J. Grodzinsky. Stimulation of aggrecan synthesis in cartilage explants by cyclic loading is localized to regions of high interstitial fluid flow. Arch. Biochem. Biophys. 366:1-7, 1999.

    Google Scholar 

  10. Chen, H.-C., and J.-L. Guan. Association of focal adhesion kinase with its potential substrate phosphotidylinositol 3-kinase. Proc. Natl. Acad. Sci. U.S.A. 91:10148-10152, 1994.

    Google Scholar 

  11. Chikama, T., M. Nakamura, and T. Nishida. Upregulation of integrin alpha5 by a C-terminus four-amino-acid sequence of substance P (phenylalanine-glycine-leucine-methionine-amide) synergistically with insulin-like growth factor-1 in SV-40 transformed human corneal epithelial cells. Biochem. Biophys. Res. Commun. 255:692-697, 1999.

    Google Scholar 

  12. Chong, L. D., A. Traynor-Kaplan, G. M. Bokoch, and M. A. Schwartz. The small GTP-binding protein Rho regulates a phosphatidylinositol 4-phosphate 5-kinase in mammalian cells. Cell 79:507-513, 1994.

    Google Scholar 

  13. Clancy, R. M., J. Rediske, X. Tang, N. Nijher, S. Frenkel, M. Philips, and S. B. Abramson. Outside-in signaling in the chondrocyte. Nitric oxide disrupts fibronectin-induced assembly of a subplasmalemmal actin/rho A/focal adhesion kinase signaling complex. J. Clin. Invest. 100:1789-1796, 1997.

    Google Scholar 

  14. Dedhar, S. Cell–substrate interactions and signaling through ILK. Curr. Opin. Cell Biol. 12:250-256, 2000.

    Google Scholar 

  15. Duncan, R. L., and C. H. Turner. Mechanotransduction and the functional response of bone to mechanical strain. Calcif. Tissue Int. 57:344-358, 1995.

    Google Scholar 

  16. Enomoto-Iwamoto, M., M. Iwamoto, K. Nakashima, Y. Mukudai, D. Boettiger, M. Pacifici, K. Kurisu, and F. Suzuki. Involvement of alpha5beta1 integrin in matrix interactions and proliferation of chondrocytes. J. Bone Miner. Res. 12:1124-1132, 1997.

    Google Scholar 

  17. Fanning, P. J., G. Emkey, R. J. Smith, A. J. Grodzinsky, N. Szasz, and S. B. Tippel. Mechanical regulation of mitogen-activated protein kinase signaling in articular cartilage. J. Biol. Chem. 278:50940-50948, 2003.

    Google Scholar 

  18. Giancotti, F. G., and E. Ruoslahti. Integrin signaling. Science 285:1028-1032, 1999.

    Google Scholar 

  19. Graff, R., S. Kelley, and G. Lee. Role of pericellular matrix in development of a mechanically functional neocartilage. Biotechnol. Bioeng. 82:457-464, 2003.

    Google Scholar 

  20. Guilak, F., W. R. Jones, H. P. Ting-Beall, and G. M. Lee. The deformation behavior and mechanical properties of chondrocytes in articular cartilage. Osteoarthritis Cartilage 7:59-70, 1999.

    Google Scholar 

  21. Guilak, F., R. A. Zell, G. R. Erickson, D. A. Grande, C. T. Rubin, K. J. McLeod, and H. J. Donahue. Mechanically induced calcium waves in articular chondrocytes are inhibited by gadolinium and amiloride. J. Orthop. Res. 17:421-429, 1999

    Google Scholar 

  22. Hamanishi, C., M. Hashima, H. Satsuma, and S. Tanaka. Protein kinase C activator inhibits progression of osteoarthritis induced in rabbit knee joints. J. Lab. Clin. Med. 127:540-544, 1996.

    Google Scholar 

  23. Han, O., T. Takei, M. Basson, and B. E. Sumpio. Translocation of PKC isoforms in bovine aortic smooth muscle cells exposed to strain. J. Cell. Biochem. 80:367-372, 2001.

    Google Scholar 

  24. Helminen, H. J., A. M. Saamanen, J. Jurvelin, I. Kiviranta, J. J. Parkkinen, M. J. Lammi, and M. Tammi. The effect of loading on articular cartilage. Duodecim 108:1097-1107, 1992.

    Google Scholar 

  25. Hildebrand, J. D., M. D. Schaller, and J. T. Parsons. Paxillin, a tyrosine-phosphorylated focal adhesion-associated protein binds to the carboxyl terminal domain of focal adhesion kinase. Mol. Cell. Biol. 6:637-647, 1995.

    Google Scholar 

  26. Holmvall, K., L. Camper, S. Johansson, J. H. Kimura, and E. Lundgren-Akerlund. Chondrocyte and chondrosarcoma cell integrins with affinity for collagen type II and their responses to mechanical stress. Exp. Cell Res. 221:496-503, 1995.

    Google Scholar 

  27. Horwitz, A., K. Duggan, C. Buck, M. Beckeri, and K. Burridge. Interactions of plasma membrane fibronectin receptor with talin—a transmembrane linkage. Nature 320:531-533, 1986.

    Google Scholar 

  28. Hynes, R. O. Integrins: Versatility, modulation and signaling in cell adhesion. Cell 69:11-25, 1992.

    Google Scholar 

  29. Ivaska, J., L. Bosca, and P. J. Parker. PKCɛ is a permissive link in integrin-dependent IFNγ signaling that facilitates JAK phosphorylation of STAT1. Nat. Cell Biol. 5:363-369, 2003.

    Google Scholar 

  30. Jalial, S., M. A. del Pozo, K.-D. Chen, H. Miao, Y.-S. Li, M. A. Schwartz, J. Y.-J. Shyy, and S. Chien. Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands. Proc. Natl. Acad. Sci. U.S.A. 98:1042-1046, 2001.

    Google Scholar 

  31. Jin, M., E. H. Frank, T. M. Quinn, E. B. Hunziker, A. J. Grodzinsky. Tissue shear deformation stimulates proteoglycan and protein biosynthesis in bovine cartilage explants. Arch. Biochem. Biophys. 395:41-48, 2001.

    Google Scholar 

  32. Jobanputra, P., L. Hong, K. Jenkins, C. Bavington, F. R. Brennan, G. Nuki, J. L. Godolphin, and D. M. Salter. Modulation of human chondrocyte integrins by inflammatory synovial fluid. Arthritis Rheum. 39:1430-1432, 1996.

    Google Scholar 

  33. Jones, K. L., M. Brown, S. Y. Ali, and R. A. Brown. An immunohistochemical study of fibronectin in human osteoarthritic and disease free articular cartilage. Ann. Rheum. Dis. 46:809-815, 1987.

    Google Scholar 

  34. Kiviranta, I., M. Tammi, J. Jurvelin, J. Arokoski, A.-M. Saamanen, and H. Helminen. Moderate running exercise augments glycosaminoglycans and thickness of articular cartilage in the knee joint of young beagle dogs. J. Orthop. Res. 6:188-195, 1988.

    Google Scholar 

  35. Knight, M. M., D. A. Lee, and D. L. Bader. The influence of elaborated pericellular matrix on the deformation of isolated articular chondrocytes cultured in agarose. Biochim. Biophys. Acta 1405:67-77, 1998.

    Google Scholar 

  36. Knight, M. M., J. M. Ross, A. F. Sherwin, D. A. Lee, D. L. Bader, and C. A. Poole. Chondrocyte deformation within mechanically and enzymatically extracted chondrons compressed in agarose. Biochim. Biophys. Acta—Gen. Subj. 1526:141-146, 2001.

    Google Scholar 

  37. Kolanus, W., and B. Seed. Integrins and inside-out signal transduction: converging signals from PKC and PIP3. Curr. Biol. 9:725-731, 1997.

    Google Scholar 

  38. Kuo, H.-P., H.-C. Lin, K.-H. Hwang, C.-H. Wang, and L.-C. Lu. Lipopolysaccharide enhances substance P-mediated neutrophil adherence to epithelial cells and cytokine release. Am. J. Respir. Crit. Care Med. 1891-1897, 2000.

  39. Lapadula, G., F. Iannone, C. Zuccaro, V. Grattagliano, M. Covelli, V. Patella, G. Lo Bianco, and V. Pipitone. Chrondrocyte phenotyping in human osteoarthritis. Clin. Rheumatol. 17:99-104, 1998.

    Google Scholar 

  40. Lee, D. A., T. Noguchi, S. P. Frean, P. Lees, and D. L. Bader. The influence of mechanical loading on isolated chondrocytes seeded in agarose constructs. Biorheology 37:149-161, 2000.

    Google Scholar 

  41. Lee, H.-S., S. J. Millward-Sadler, M. O. Wright, G. Nuki, R. Al-Jamal, and D. M. Salter. Activation of integrin—RACK1/PKC association in human articular chondrocyte mechanotransduction. Osteoarthritis Cartilage 10:890-897, 2002.

    Google Scholar 

  42. Lee, H.-S., S. J. Millward-Sadler, M. O. Wright, G. Nuki, and D. M. Salter. Integrin and mechanosensitive ion channel-dependent tyrosine phosphorylation of focal adhesion proteins and-catenin in human articular chondrocytes after mechanical stimulation. J. Bone Miner. Res. 15:1501-1509, 2000.

    Google Scholar 

  43. Lin, T. H., A. E. Aplin, Y. Shen, Q. Chen, M. Schaller, L. Romer, I. Aukhil, and R. L. Juliano. Integrin-mediated activation of MAP kinase is independent of FAK: Evidence for dual integrin signaling pathways in fibroblasts. J. Cell Biol. 136:1385-1395, 1997.

    Google Scholar 

  44. Loeser, R. F. Chondrocyte integrin expression and function. Biorheology 37:109-116, 2000.

    Google Scholar 

  45. Loeser, R. F. Growth factor regulation of chondrocyte integrins. Arthritis Rheum. 40:270-276, 1997.

    Google Scholar 

  46. Loeser, R. F., C. S. Carlson, and M. P. McGee. Expression of beta 1 integrins by cultured articular chondrocytes and in osteoarthritic cartilage. Exp. Cell. Res. 217:248-257, 1995.

    Google Scholar 

  47. Lotz, M., J. H. Vaughan, and D. A. Crason. Effect of neuropeptides on production of inflammatory cytokines by human monocytes. Science 241:1218-1220, 1988.

    Google Scholar 

  48. Malek, A. M., and S. Izumo. Mechanism of endothelial cell shape change and cytoskeletal remodeling in response to fluid shear stress. J. Cell Sci. 109:713-726, 1996.

    Google Scholar 

  49. Mills, I., C. R. Cohen, K. Kamal, G. Li, T. Shin, W. Du, and B. E. Sumpio. Strain activation of bovine aortic smooth muscle cell proliferation and alignment: Study of strain dependency and the role of protein kinase A and C signaling pathways. J. Cell Physiol. 170:228-234, 1997.

    Google Scholar 

  50. Millward-Sadler, S. J., A. Mackenzie, M. O. Wright, H.-S. Lee, K. Elliot, L. Gerrard, C. E. Fiskerstrand, D. M. Salter, and J. P. Quinn. Tachykinin expression in cartilage and function in human articular chondrocyte mechanotransduction. Arthritis Rheum. 48:146-156, 2003.

    Google Scholar 

  51. Millward-Sadler, S. J., M. O. Wright, L. W. Davies, G. Nuki, and D. M. Salter. 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, 2000.

    Google Scholar 

  52. Millward-Sadler, S. J., M. O. Wright, H.-S. Lee, H. Caldwell, G. Nuki, and D. M. Salter. Altered electrophysiological responses to mechanical stimulation and abnormal signaling through 5 1 integrin in chondrocytes from osteoarthritic cartilage. Osteoarthritis Cartilage 8:272-278, 2000.

    Google Scholar 

  53. Millward-Sadler, S. J., M. O. Wright, H.-S. Lee, K. Nishida, H. Caldwell, G. Nuki, and D. M. Salter. Integrin-regulated secretion of interleukin 4: A novel pathway of mechanotransduction in human articular chondrocytes. J. Cell Biol. 145:183-189, 1999.

    Google Scholar 

  54. Miyamoto, S., H. Teramoto, J. S. Gutkind, and K. M. Yamada. Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: Roles of integrin aggregation and occupancy of receptors. J. Cell Biol. 135:1633-1645, 1996.

    Google Scholar 

  55. Moro, L., M. Venturino, C. Bozzo, L. Silengo, F. Altruda, L. Beguinot, G. Tarone, and P. Defilippi. Integrins induce activation of the EGF receptor: Role in MAP kinase induction and adhesion dependent cell survival. EMBO J. 17:6622-6632, 1998.

    Google Scholar 

  56. Nakamura, M., T. Nagano, T. Chikama, and T. Nishida. Upregulation of phosphorylation of focal adhesion kinase and paxillin by combination of substance P and IGF-1 in SV-40 transformed human corneal epithelial cells. Biochem. Biophys. Res. Commun. 242:16-20, 1998.

    Google Scholar 

  57. Naruse, K., T. Yamada, X. R. Sai, M. Hamaguchi, and M. Sokabe. pp125FAK is required for stretch dependent morphological response of endothelial cells. Oncogene 17:455-463, 1998.

    Google Scholar 

  58. Osborn, K., S. Trippel, and H. Mankin. Growth factor stimulation of adult articular cartilage. J. Orthop. Res. 7:35-42, 1989.

    Google Scholar 

  59. Ostergaard, K., D. M. Salter, C. B. Andersen, J. Petersen, and K. Bendtzen. CD44 expression is up-regulated in the deep zone of osteoarthritic cartilage from human femoral heads. Histopathology 31:451-459, 1997.

    Google Scholar 

  60. Ostergaard, K., D. M. Salter, J. Petersen, K. Bendtzen, J. Hvolris, and C. B. Andersen. Expression of α-and β-subunits of the integrin superfamily in articular cartilage from macroscopically normal and osteoarthritic human femoral heads. Ann. Rheum. Dis. 57:303-308, 1998.

    Google Scholar 

  61. Otey, C. A., and K. Burridge. Patterning of the membrane cytoskeleton by the extracellular matrix. Sem in. Cell Biol. 1:391-399, 1990.

    Google Scholar 

  62. Paukkonen, K., K. Selkainaho, J. Jurvelin, and H. J. Helminen. Cells and nuclei of articular cartilage chondrocytes in young rabbits enlarged after nonstrenuous physical exercise. J. Anat. 142:13-20, 1985.

    Google Scholar 

  63. Pavasant, P., T. Shizari, and C. Underhill. Hyaluronan synthesis by epiphysial chondrocytes is regulated by growth hormone, insulin-like growth factor-1, parathyroid hormone and transforming growth factor-beta 1. Matrix Biol. 15:423-432, 1996.

    Google Scholar 

  64. Ren, X. D., G. M. Bokoch, A. Traynor-Kaplan, G. H. Jenkins, R. A. Anderson, and M. A. Schwartz. Physical association of the small GTPase Rho with a 68 kDa phosphatidylinositol 4-phosphate 5-kinase in Swiss 3T3 cells. Mol. Cell. Biol. 7:435-442, 1996.

    Google Scholar 

  65. Roberts, S., B. Weightman, J. P. G. Urban, and D. Chapell. Mechanical and biochemical properties of human articular cartilage in osteoarthritic femoral heads and in autopsy specimens. J. Bone Joint Surg. 68:278-288, 1986.

    Google Scholar 

  66. Ruwhof, C., and A. van der Laarse. Mechanical stress-induced cardiac hypertrophy: Mechanisms and signal transduction pathways. Cardiovasc. Res. 47:23-37, 2000.

    Google Scholar 

  67. Sadoshima, J., and S. Izumo. Mechanical stretch rapidly activates multiple signal transduction pathways in cardiac myocytes: Potential involvement of an autocrine/paracrine mechanism. EMBO J. 12:1681-1692, 1993.

    Google Scholar 

  68. Salter, D. M., J. E. Robb, and M. O. Wright. Electrophysiological responses of human bone cells to mechanical stimulation: Evidence for specific integrin function in mechanotransduction. J. Bone Miner. Res. 12:1133-1141, 1997.

    Google Scholar 

  69. Santala, P., and J. Heino. Regulation of integrin-type cell adhesion receptors by cytokines. J. Biol. Chem. 266:23505-23509, 1991.

    Google Scholar 

  70. Sauerland, K., R. X. Raiss, and J. Steinmeyer. Proteoglycan metabolism and viability of articular cartilage explants as modulated by the frequency of intermittent loading. Osteoarthritis Cartilage 11:343-350, 2003.

    Google Scholar 

  71. Schaller, M. D., J. D. Hildebrand, J. D. Shannon, J. W. Fox, R. R. Vines, and J. T. Parsons. Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src. Mol. Cell. Biol. 14:1680-1688, 1994.

    Google Scholar 

  72. Schlaepfer, D. D., M. A. Broome, and T. Hunter. Fibronectin-stimulated signaling from a focal adhesion kinase-c-Src complex: Involvement of the Grb2, p130cas, and Nck adaptor proteins. Mol. Cell. Biol. 17:1702-1713, 1997.

    Google Scholar 

  73. Schlaepfer, D. D., S. Hanks, T. Hunter, and P. van der Greer. Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase. Nature 372:786-791, 1994.

    Google Scholar 

  74. Schneller, M., K. Vuori, and E. Ruoslahti. αVβ3 integrin associates with activated insulin and PDGFb receptors and potentiates the biological activity of PDGF. EMBO J. 16:5600-5607, 1997.

    Google Scholar 

  75. Schwartz, M. A. Integrin signaling revisited. Trends Cell Biol. 11:466-470, 2001.

    Google Scholar 

  76. Schwartz, M. A., and V. Baron. Interactions between mitogenic stimuli, or a thousand and one connections. Curr. Opin. Cell Biol. 11:197-202, 1999.

    Google Scholar 

  77. Short, S. M., J. L. Boyer, and R. L. Juliano. Integrins regulate the linkage between upstream and downstream events in G-protein-coupled receptor signaling to mitogen-activated protein kinase. J. Biol. Chem. 275:12970-12977, 2000.

    Google Scholar 

  78. Short, S. M., G. A. Talbott, and R. L. Juliano. Integrin-mediated signaling events in human endothelial cells. Mol. Biol. Cell 9:1969-1980, 1998.

    Google Scholar 

  79. Shyy, J. Y.-J., and S. Chien. Role of integrins in cellular responses to mechanical stress and adhesion. Curr. Opin. Cell Biol. 9:707-713, 1997.

    Google Scholar 

  80. Slowman, S. D., and K. D. Brandt. Composition and glycosaminoglycan metabolism of articular cartilage from habitually loaded and habitually unloaded sites. Arthritis Rheum. 29:88-94, 1986.

    Google Scholar 

  81. Stefanovic-Ravic, M. J., J. Stadler, and C. H. Evans. Nitric oxide and arthritis. Arthritis Rheum. 36:1036-1044, 1993.

    Google Scholar 

  82. Takei, T., O. Han, M. Ikeda, P. Male, I. Mills, and B. E. Sumpio. Cyclic strain stimulates isoform-specific PKC activation and translocation in cultured human keratinocytes. J. Cell. Biochem. 67:327-337, 1997.

    Google Scholar 

  83. Taskiran, D., M. J. Stefanovic-Ravic, H. Georgescu, and C. H. Evans. Nitric oxice mediates suppression of cartilage proteoglycan synthesis by interleukin-1. Biochem. Biophys. Res. Commun. 200:142-148, 1994.

    Google Scholar 

  84. Urban, J. P. G. The chondrocyte: A cell under pressure. Br. J. Rheumatol. 33:901-908, 1994.

    Google Scholar 

  85. Valhmu, W. B., E. J. Stazzone, N. M. Bachrach, F. Saed-Nejad, S. G. Fischer, V. C. Mow, and A. Ratcliffe. Load-controlled compression of articular cartilage induces a transient stimulation of aggrecan gene expression. Arch. Biochem. Biophys. 353:29-36, 1998.

    Google Scholar 

  86. Veldhuijzen, J. P., L. A. Bourret, and G. A. Rodan. In vitro studies of the effect of intermittent compressive forces on cartilage cell proliferation. J. Cell. Physiol. 98:299-306, 1979.

    Google Scholar 

  87. Vuori, K., H. Hirai, S. Aizawa, and E. Ruoslahti. Introduction of p130cas signaling complex formation upon integrin-mediated cell adhesion: A role for Src family kinases. Mol. Cell. Biol. 16:2606-2613, 1996.

    Google Scholar 

  88. Waldman, S. D., C. G. Spiteri, M. D. Grynpas, R. M. Pilliar, J. Hong, and R. A. Kandel. Effect of biomechanical conditioning on cartilaginous tissue formation in vitro. J. Bone Joint Surg. Am. 85:101-105, 2003.

    Google Scholar 

  89. Wang, N., J. P. Butler, and D. E. Ingber. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260:1124-1127, 1993.

    Google Scholar 

  90. Wright, M. O., J. L. Godolphin, E. Dunne, C. Bavington, P. Jobanputra, G. Nuki, and D. M. Salter. Hyperpolarisation of cultured human chondrocytes following cyclical pressurisation involves α5β1 integrin and integrin-associated intracellular pathways. J. Orthop. Res. 15:742-747, 1997.

    Google Scholar 

  91. Wright, M. O., P. Jobanputra, C. Bavington, D. M. Salter, and G. Nuki. The effects of intermittent pressurisation on the electrophysiology of cultured human articular chondrocytes: Evidence for the presence of stretch-activated membrane ion channels. Clin. Sci. 90:61-71, 1996.

    Google Scholar 

  92. Wright, M. O., R. Stockwell, and G. Nuki. Response of plasma membrane to applied hydrostatic pressure in chondrocytes and fibroblasts. Connect. Tissue Res. 28:49-70, 1992.

    Google Scholar 

  93. Wu, Q. Q., and Q. Chen. Mechanoregulation of chondrocyte proliferation, maturation, and hypertrophy: Ion-channel dependent transduction of matrix deformation signals. Exp. Cell Res. 156:383-391, 2000

    Google Scholar 

  94. Yonezawa, Y., K. Kato, H. Yagita, Y. Yamauchi, and K. Okumura. VLA-5-mediated interaction with fibronectin induces cytokine production by human chondrocytes. Biochem. Biophys. Res. Commun. 219:261-265, 1996.

    Google Scholar 

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  1. Osteoarticular Research Group, Division of Pathology, School of Molecular and Clinical Medicine, College of Medicine and Veterinary Medicine, Edinburgh University Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom

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Millward-Sadler, S.J., Salter, D.M. Integrin-Dependent Signal Cascades in Chondrocyte Mechanotransduction. Annals of Biomedical Engineering 32, 435–446 (2004). https://doi.org/10.1023/B:ABME.0000017538.72511.48

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