• 1
    Stockwell RA. Structure and function of the chondrocyte under mechanical stress. In: HelminenHJ, KivirantaI, TammiM, SaamanenAM, PaukkonenK, JurvelinJ, editors. Joint loading: biology and health of articular structures. Bristol: John Wright & Sons; 1987. p. 12648.
  • 2
    Van Campen GP, van de Stadt RJ. Cartilage and chondrocytes responses to mechanical loading in vitro. In: HelminenHJ, KivirantaI, TammiM, SaamanenAM, PaukkonenK, JurvelinJ, editors. Joint loading: biology and health of articular structures. Bristol: John Wright & Sons; 1987. p. 11225.
  • 3
    Guilak F, Sah RL, Setton LA. Physical regulation of cartilage metabolism. In: MowVC, HayesWC, editors. Basic orthopaedic biomechanics. 2nd ed. Philadelphia: Lippincott-Raven; 1997. p. 179207.
  • 4
    Poole CA. Chondrons, the chondrocyte and its pericellular microenvironment. In: KuettnerKE, SchleyerbachR, PeyronJG, HascallVC, editors. Articular cartilage and osteoarthritis. New York: Raven Press; 1992. p. 20120.
  • 5
    Poole CA. Articular cartilage chondrons: form, function and failure. J Anat 1997; 191(Pt 1): 113.
  • 6
    Szirmai JA. The concept of the chondron as a biomechanical unit. In: HartmannF, editor. Biopolymer und Biomechanik von Bindegewebssystemen. Berlin: Academic Press; 1974. p. 8791.
  • 7
    Benninghoff A. Form und bau der Gelenkknorpel in ihren Beziehungen Zur Funktion. Zweiter teil: der Aufbau des Gelenkknorpels in sienen Bezienhungen zur Funktion. Z Zellforsch Mikrop Anat 1925; 2: 783862.
  • 8
    Poole CA, Gilbert RT, Herbage D, Hartmann DJ. Immunolocalization of type IX collagen in normal and spontaneously osteoarthritic canine tibial cartilage and isolated chondrons. Osteoarthritis Cartilage 1997; 5: 191204.
  • 9
    Guilak F, Alexopoulos LG, Upton ML, Youn I, Choi JB, Cao L, et al. The pericellular matrix as a transducer of biomechanical and biochemical signals in articular cartilage. Ann N Y Acad Sci 2006; 1068: 498512.
  • 10
    Adams JC, Watt FW. Regulation of development and differentiation by the extracellular matrix. Development 1993; 117: 118398.
  • 11
    Boudreau N, Myers C, Bissel MJ. From laminin to lamin: regulation of tissue-specific gene expression by the ECM. Trends Cell Biol 1995; 5: 14.
  • 12
    Loeser RF. Growth factor regulation of chondrocyte integrins: differential effects of insulin-like growth factor 1 and transforming growth factor β on α1β1 integrin expression and chondrocyte adhesion to type VI collagen. Arthritis Rheum 1997; 40: 2706.
  • 13
    Ruoslahti E, Yamaguchi Y. Proteoglycans as modulators of growth factor activities. Cell 1991; 64: 8679.
  • 14
    Sandy JD, O'Neill JR, Ratzlaff LC. Acquisition of hyaluronate-binding affinity in vivo by newly synthsized cartilage proteoglycans. Biochem J 1989; 258: 87580.
  • 15
    Poole CA, Flint MH, Beaumont BW. Chondrons extracted from canine tibial cartilage: preliminary report on their isolation and structure. J Orthop Res 1988; 6: 40819.
  • 16
    Choi JB, Youn I, Cao L, Leddy HA, Gilchrist CL, Setton LA, et al. Zonal changes in the three-dimensional morphology of the chondron under compression: the relationship among cellular, pericellular, and extracellular deformation in articular cartilage. J Biomech 2007; 40: 2596603.
  • 17
    Lee V, Cao L, Zhang Y, Kiani C, Adams ME, Yang BB. The roles of matrix molecules in mediating chondrocyte aggregation, attachment, and spreading. J Cell Biochem 2000; 79: 32233.
  • 18
    Loeser RF, Sadiev S, Tan L, Goldring MB. Integrin expression by primary and immortalized human chondrocytes: evidence of a differential role for α1β1 and α2β1 integrins in mediating chondrocyte adhesion to types II and VI collagen. Osteoarthritis Cartilage 2000; 8: 96105.
  • 19
    Knudson W, Loeser RF. CD44 and integrin matrix receptors participate in cartilage homeostasis. Cell Mol Life Sci 2002; 59: 3644.
  • 20
    McDevitt CA, Marcelino J, Tucker L. Interaction of intact type VI collagen with hyaluronan. FEBS Lett 1991; 294: 16770.
  • 21
    Buschmann MD, Gluzband YA, Grodzinsky AJ, Hunziker EB. Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture. J Cell Sci 1995; 108(Pt 4): 1497508.
  • 22
    Timpl R, Engel J. Type VI collagen. In: MayneR, BurgesonRE, editors. Structure and function of collagen types. New York: Academic Press; 1987. p. 10543.
  • 23
    Wiberg C, Hedbom E, Khairullina A, Lamande SR, Oldberg A, Timpl R, et al. Biglycan and decorin bind close to the n-terminal region of the collagen VI triple helix. J Biol Chem 2001; 276: 1894752.
  • 24
    Bidanset DJ, Guidry C, Rosenberg LC, Choi HU, Timpl R, Hook M. Binding of the proteoglycan decorin to collagen type VI. J Biol Chem 1992; 267: 52506.
  • 25
    Tillet E, Wiedemann H, Golbik R, Pan TC, Zhang RZ, Mann K, et al. Recombinant expression and structural and binding properties of α1(VI) and α2(VI) chains of human collagen type VI [published erratum appears in Eur J Biochem 1994;222:1064]. Eur J Biochem 1994; 221: 17785.
  • 26
    Specks U, Mayer U, Nischt R, Spissinger T, Mann K, Timpl R, et al. Structure of recombinant N-terminal globule of type VI collagen α3 chain and its binding to heparin and hyaluronan. EMBO J 1992; 11: 428190.
  • 27
    Bonaldo P, Russo V, Bucciotti F, Doliana R, Colombatti A. Structural and functional features of the α3 chain indicate a bridging role for chicken collagen VI in connective tissues. Biochemistry 1990; 29: 124554.
  • 28
    Pfaff M, Aumailley M, Specks U, Knolle J, Zerwes HG, Timpl R. Integrin and Arg-Gly-Asp dependence of cell adhesion to the native and unfolded triple helix of collagen type VI. Exp Cell Res 1993; 206: 16776.
  • 29
    Aumailley M, Mann K, von der Mark H, Timpl R. Cell attachment properties of collagen type VI and Arg-Gly-Asp dependent binding to its α2(VI) and α3(VI) chains. Exp Cell Res 1989; 181: 46374.
  • 30
    Burg MA, Tillet E, Timpl R, Stallcup WB. Binding of the NG2 proteoglycan to type VI collagen and other extracellular matrix molecules. J Biol Chem 1996; 271: 261106.
  • 31
    Lamande SR, Morgelin M, Adams NE, Selan C, Allen JM. The C5 domain of the collagen VI α3(VI) chain is critical for extracellular microfibril formation and is present in the extracellular matrix of cultured cells. J Biol Chem 2006; 281: 1660714.
  • 32
    Buckwalter JA, Mankin HJ. Articular cartilage: tissue design and chondrocyte-matrix interactions. Instr Course Lect 1998; 47: 47786.
  • 33
    Marcelino J, McDevitt CA. Attachment of articular cartilage chondrocytes to the tissue form of type VI collagen. Biochim Biophys Acta 1995; 1249: 1808.
  • 34
    Sherwin AF, Carter DH, Poole CA, Hoyland JA, Ayad S. The distribution of type VI collagen in the developing tissues of the bovine femoral head. Histochem J 1999; 31: 62332.
  • 35
    Keene DR, Engvall E, Glanville RW. Ultrastructure of type VI collagen in human skin and cartilage suggests an anchoring function for this filamentous network. J Cell Biol 1988; 107: 19952006.
  • 36
    Kielty CM, Whittaker SP, Grant ME, Shuttleworth CA. Type VI collagen microfibrils: evidence for a structural association with hyaluronan. J Cell Biol 1992; 118: 97990.
  • 37
    Chang J, Nakajima H, Poole CA. Structural colocalisation of type VI collagen and fibronectin in agarose cultured chondrocytes and isolated chondrons extracted from adult canine tibial cartilage. J Anat 1997; 190(Pt 4): 52332.
  • 38
    Bonaldo P, Braghetta P, Zanetti M, Piccolo S, Volpin D, Bressan GM. Collagen VI deficiency induces early onset myopathy in the mouse: an animal model for Bethlem myopathy. Hum Mol Genet 1998; 7: 213540.
  • 39
    Carlson CS, Guilak F, Vail TP, Gardin JF, Kraus VB. Synovial fluid biomarker levels predict articular cartilage damage following complete medial meniscectomy in the canine knee. J Orthop Res 2002; 20: 92100.
  • 40
    Rivas R, Shapiro F. Structural stages in the development of the long bones and epiphyses: a study in the New Zealand white rabbit. J Bone Joint Surg Am 2002; 84-A: 85100.
  • 41
    Fink C, Cooper HJ, Huebner JL, Guilak F, Kraus VB. Precision and accuracy of a transportable dual-energy X-ray absorptiometry unit for bone mineral measurements in guinea pigs. Calcif Tissue Int 2002; 70: 1649.
  • 42
    Cao L, Youn I, Guilak F, Setton LA. Compressive properties of mouse articular cartilage determined in a novel micro-indentation test method and biphasic finite element model. J Biomech Eng 2006; 128: 76671.
  • 43
    Hayes WC, Keer LM, Herrmann G, Mockros LF. A mathematical analysis for indentation tests of articular cartilage. J Biomech 1972; 5: 54151.
  • 44
    Alexopoulos LG, Haider MA, Vail TP, Guilak F. Alterations in the mechanical properties of the human chondrocyte pericellular matrix with osteoarthritis. J Biomech Eng 2003; 125: 32333.
  • 45
    Hochmuth RM. Micropipette aspiration of living cells. J Biomech 2000; 33: 1522.
  • 46
    Trickey WR, Vail TP, Guilak F. The role of the cytoskeleton in the viscoelastic properties of human articular chondrocytes. J Orthop Res 2004; 22: 1319.
  • 47
    Guilak F, Erickson GR, Ting-Beall HP. The effects of osmotic stress on the viscoelastic and physical properties of articular chondrocytes. Biophys J 2002; 82: 7207.
  • 48
    Guilak F, Alexopoulos LG, Haider MA, Ting-Beall HP, Setton LA. Zonal uniformity in mechanical properties of the chondrocyte pericellular matrix: micropipette aspiration of canine chondrons isolated by cartilage homogenization. Ann Biomed Eng 2005; 33: 13128.
  • 49
    Alexopoulos LG, Williams GM, Upton ML, Setton LA, Guilak F. Osteoarthritic changes in the biphasic mechanical properties of the chondrocyte pericellular matrix in articular cartilage. J Biomech 2005; 38: 50917.
  • 50
    Guilak F, Ratcliffe A, Lane N, Rosenwasser MP, Mow VC. Mechanical and biochemical changes in the superficial zone of articular cartilage in canine experimental osteoarthritis. J Orthop Res 1994; 12: 47484.
  • 51
    Setton LA, Mow VC, Muller FJ, Pita JC, Howell DS. Mechanical properties of canine articular cartilage are significantly altered following transection of the anterior cruciate ligament. J Orthop Res 1994; 12: 45163.
  • 52
    Guilak F, Mow VC. The mechanical environment of the chondrocyte: a biphasic finite element model of cell-matrix interactions in articular cartilage. J Biomech 2000; 33: 166373.
  • 53
    Alexopoulos LG, Setton LA, Guilak F. The biomechanical role of the chondrocyte pericellular matrix in articular cartilage. Acta Biomater 2005; 1: 31725.
  • 54
    Youn I, Choi JB, Cao L, Setton LA, Guilak F. Zonal variations in the three-dimensional morphology of the chondron measured in situ using confocal microscopy. Osteoarthritis Cartilage 2006; 14: 88997.
  • 55
    Leipzig ND, Athanasiou KA. Static compression of single chondrocytes catabolically modifies single-cell gene expression. Biophys J 2008; 94: 241222.
  • 56
    Han Y, Cowin SC, Schaffler MB, Weinbaum S. Mechanotransduction and strain amplification in osteocyte cell processes. Proc Natl Acad Sci U S A 2004; 101: 1668994.
  • 57
    Weinbaum S, Guo P, You L. A new view of mechanotransduction and strain amplification in cells with microvilli and cell processes. Biorheology 2001; 38: 11942.
  • 58
    You L, Cowin SC, Schaffler MB, Weinbaum S. A model for strain amplification in the actin cytoskeleton of osteocytes due to fluid drag on pericellular matrix. J Biomech 2001; 34: 137586.
  • 59
    Pepe G, Lucarini L, Zhang RZ, Pan TC, Giusti B, Quijano-Roy S, et al. COL6A1 genomic deletions in Bethlem myopathy and Ullrich muscular dystrophy. Ann Neurol 2006; 59: 1905.
  • 60
    Lampe AK, Bushby KM. Collagen VI related muscle disorders. J Med Genet 2005; 42: 67385.
  • 61
    Griffiths MR, Shepherd M, Ferrier R, Schuppan D, James OF, Burt AD. Light microscopic and ultrastructural distribution of type VI collagen in human liver: alterations in chronic biliary disease. Histopathology 1992; 21: 33544.
  • 62
    Higuchi I, Shiraishi T, Hashiguchi T, Suehara M, Niiyama T, Nakagawa M, et al. Frameshift mutation in the collagen VI gene causes Ullrich's disease. Ann Neurol 2001; 50: 2615.
  • 63
    Pan TC, Zhang RZ, Sudano DG, Marie SK, Bonnemann CG, Chu ML. New molecular mechanism for Ullrich congenital muscular dystrophy: a heterozygous in-frame deletion in the COL6A1 gene causes a severe phenotype. Am J Hum Genet 2003; 73: 35569.
  • 64
    Ljubimov AV, Burgeson RE, Butkowski RJ, Couchman JR, Wu RR, Ninomiya Y, et al. Extracellular matrix alterations in human corneas with bullous keratopathy. Invest Ophthalmol Vis Sci 1996; 37: 9971007.
  • 65
    Mollnau H, Munkel B, Schaper J. Collagen VI in the extracellular matrix of normal and failing human myocardium. Herz 1995; 20: 8994.
  • 66
    Rauch A, Pfeiffer RA, Trautmann U. Deletion or triplication of the α3 (VI) collagen gene in three patients with 2q37 chromosome aberrations and symptoms of collagen-related disorders. Clin Genet 1996; 49: 27985.
  • 67
    Specks U, Nerlich A, Colby TV, Wiest I, Timpl R. Increased expression of type VI collagen in lung fibrosis. Am J Respir Crit Care Med 1995; 151: 195664.
  • 68
    Takasaki S, Fujiwara S, Shinkai H, Ooshima A. Human type VI collagen: purification from human subcutaneous fat tissue and an immunohistochemical study of morphea and systemic sclerosis. J Dermatol 1995; 22: 4805.
  • 69
    Ballock RT, O'Keefe RJ. Physiology and pathophysiology of the growth plate. Birth Defects Res Part C Embryo Today 2003; 69: 12343.
  • 70
    Tanaka T, Ikari K, Furushima K, Okada A, Tanaka H, Furukawa K, et al. Genomewide linkage and linkage disequilibrium analyses identify COL6A1, on chromosome 21, as the locus for ossification of the posterior longitudinal ligament of the spine. Am J Hum Genet 2003; 73: 81222.
  • 71
    Quarto R, Dozin B, Bonaldo P, Cancedda R, Colombatti A. Type VI collagen expression is upregulated in the early events of chondrocyte differentiation. Development 1993; 117: 24551.
  • 72
    Atkinson JC, Ruhl M, Becker J, Ackermann R, Schuppan D. Collagen VI regulates normal and transformed mesenchymal cell proliferation in vitro. Exp Cell Res 1996; 228: 28391.
  • 73
    Mylona P, Kielty CM, Hoyland JA, Aplin JD. Expression of type VI collagen mRNAs in human endometrium during the menstrual cycle and first trimester of pregnancy. J Reprod Fertil 1995; 103: 15967.
  • 74
    Sloan P, Carter DH, Kielty CM, Shuttleworth CA. An immunohistochemical study examining the role of collagen type VI in the rodent periodontal ligament. Histochem J 1993; 25: 52330.
  • 75
    Tsukahara S, Miyazawa N, Akagawa H, Forejtova S, Pavelka K, Tanaka T, et al. COL6A1, the candidate gene for ossification of the posterior longitudinal ligament, is associated with diffuse idiopathic skeletal hyperostosis in Japanese. Spine 2005; 30: 23214.