• 1
    Poole AR. An introduction to the pathophysiology of osteoarthritis. Front Biosci 1999; 4: D66270.
  • 2
    Pelletier JP, DiBattista JA, Roughley P, McCollum R, Martel-Pelletier J. Cytokines and inflammation in cartilage degradation. Rheum Dis Clin North Am 1993; 19: 54568.
  • 3
    Aigner T, Vornehm SI, Zeiler G, Dudhia J, von der Mark K, Bayliss MT. Suppression of cartilage matrix gene expression in upper zone chondrocytes of osteoarthritic cartilage. Arthritis Rheum 1997; 40: 5629.
  • 4
    Smith RL. Degradative enzymes in osteoarthritis. Front Biosci 1999; 4: D70412.
  • 5
    Baragi VM, Renkiewicz RR, Jordan H, Bonadio J, Hartman JW, Roessler BJ. Transplantation of transduced chondrocytes protects articular cartilage from interleukin 1-induced extracellular matrix degradation. J Clin Invest 1995; 96: 245460.
  • 6
    Nixon AJ, Haupt JL, Frisbie DD, Morisset SS, McIlwraith CW, Robbins PD, et al. Gene-mediated restoration of cartilage matrix by combination insulin-like growth factor-I/interleukin-1 receptor antagonist therapy. Gene Ther 2005; 12: 17786.
  • 7
    Pelletier JP, Caron JP, Evans C, Robbins PD, Georgescu HI, Jovanovic D, et al. In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy. Arthritis Rheum 1997; 40: 10129.
  • 8
    Frisbie DD, Ghivizzani CS, Robbins PD, Evans CH, McIlwraith CW. Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene. Gene Ther 2002; 9: 1220.
  • 9
    Grossin L, Cournil-Henrionnet C, Pinzano A, Gaborit N, Dumas D, Etienne S, et al. Gene transfer with HSP 70 in rat chondrocytes confers cytoprotection in vitro and during experimental osteoarthritis. FASEB J 2006; 20: 6575.
  • 10
    Madry H, Zurakowski D, Trippel SB. Overexpression of human insulin-like growth factor-I promotes new tissue formation in an ex vivo model of articular chondrocyte transplantation. Gene Ther 2001; 8: 14439.
  • 11
    Madry H, Emkey G, Zurakowski D, Trippel SB. Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantation. J Gene Med 2004; 6: 23845.
  • 12
    Hidaka C, Quitoriano M, Warren RF, Crystal RG. Enhanced matrix synthesis and in vitro formation of cartilage-like tissue by genetically modified chondrocytes expressing BMP-7. J Orthop Res 2001; 19: 7518.
  • 13
    Ulrich-Vinther M, Stengaard C, Schwarz EM, Goldring MB, Soballe K. Adeno-associated vector mediated gene transfer of transforming growth factor-β1 to normal and osteoarthritic human chondrocytes stimulates cartilage anabolism. Eur Cell Mater 2005; 10: 4059.
  • 14
    Venkatesan N, Barre L, Benani A, Netter P, Magdalou J, Fournel-Gigleux S, et al. Stimulation of proteoglycan synthesis by glucuronosyltransferase-I gene delivery: a strategy to promote cartilage repair. Proc Natl Acad Sci U S A 2004; 101: 1808792.
  • 15
    Bi W, Deng JM, Zhang Z, Behringer RR, de Crombrugghe B. Sox9 is required for cartilage formation. Nat Genet 1999; 22: 859.
  • 16
    Ikeda T, Kamekura S, Mabuchi A, Kou I, Seki S, Takato T, et al. The combination of SOX5, SOX6, and SOX9 (the SOX trio) provides signals sufficient for induction of permanent cartilage. Arthritis Rheum 2004; 50: 356173.
  • 17
    Bell DM, Leung KK, Wheatley SC, Ng LJ, Zhou S, Ling KW, et al. SOX9 directly regulates the type-II collagen gene. Nat Genet 1997; 16: 1748.
  • 18
    Lefebvre V, Huang W, Harley VR, Goodfellow PN, de Crombrugghe B. SOX9 is a potent activator of the chondrocyte-specific enhancer of the proα1(II) collagen gene. Mol Cell Biol 1997; 17: 233646.
  • 19
    Ng LJ, Wheatley S, Muscat GE, Conway-Campbell J, Bowles J, Wright E, et al. SOX9 binds DNA, activates transcription, and coexpresses with type II collagen during chondrogenesis in the mouse. Dev Biol 1997; 183: 10821.
  • 20
    Xie WF, Zhang X, Sakano S, Lefebvre V, Sandell LJ. Trans-activation of the mouse cartilage-derived retinoic acid-sensitive protein gene by Sox9. J Bone Miner Res 1999; 14: 75763.
  • 21
    Salminen H, Vuorio E, Saamanen AM. Expression of Sox9 and type IIA procollagen during attempted repair of articular cartilage damage in a transgenic mouse model of osteoarthritis. Arthritis Rheum 2001; 44: 94755.
  • 22
    Aigner T, Gebhard PM, Schmid E, Bau B, Harley V, Poschl E. SOX9 expression does not correlate with type II collagen expression in adult articular chondrocytes. Matrix Biol 2003; 22: 36372.
  • 23
    Arai Y, Kubo T, Fushiki S, Mazda O, Nakai H, Iwaki Y, et al. Gene delivery to human chondrocytes by an adeno associated virus vector. J Rheumatol 2000; 27: 97982.
  • 24
    Madry H, Cucchiarini M, Terwilliger EF, Trippel SB. Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage. Hum Gene Ther 2003; 14: 393402.
  • 25
    Cucchiarini M, Madry H, Ma C, Thurn T, Zurakowski D, Menger MD, et al. Improved tissue repair in articular cartilage defects in vivo by rAAV-mediated overexpression of human fibroblast growth factor 2. Mol Ther 2005; 12: 22938.
  • 26
    Xiao X, Li J, Samulski RJ. Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector. J Virol 1996; 70: 8098108.
  • 27
    Cucchiarini M, Madry H. Gene therapy for cartilage defects. J Gene Med 2005; 7: 1495509.
  • 28
    Mason JM, Grande DA, Barcia M, Grant R, Pergolizzi RG, Breitbart AS. Expression of human bone morphogenic protein 7 in primary rabbit periosteal cells: potential utility in gene therapy for osteochondral repair. Gene Ther 1998; 5: 1098104.
  • 29
    Mi Z, Ghivizzani SC, Lechman ER, Jaffurs D, Glorioso JC, Evans CH, et al. Adenovirus-mediated gene transfer of insulin-like growth factor 1 stimulates proteoglycan synthesis in rabbit joints. Arthritis Rheum 2000; 43: 256370.
  • 30
    Mankin HJ, Dorfman H, Lippiello L, Zarins A. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am 1971; 53: 52337.
  • 31
    Samulski RJ, Chang LS, Shenk T. Helper-free stocks of recombinant adeno-associated viruses: normal integration does not require viral gene expression. J Virol 1989; 63: 38228.
  • 32
    Cucchiarini M, Ren XL, Perides G, Terwilliger EF. Selective gene expression in brain microglia mediated via adeno-associated virus type 2 and type 5 vectors. Gene Ther 2003; 10: 65767.
  • 33
    Sudbeck P, Schmitz ML, Baeuerle PA, Scherer G. Sex reversal by loss of the C-terminal transactivation domain of human SOX9. Nat Genet 1996; 13: 2302.
  • 34
    Madry H, Trippel SB. Efficient lipid-mediated gene transfer to articular chondrocytes. Gene Ther 2000; 7: 28691.
  • 35
    Merrihew C, Soeder S, Rueger DC, Kuettner KE, Chubinskaya S. Modulation of endogenous osteogenic protein-1 (OP-1) by interleukin-1 in adult human articular cartilage. J Bone Joint Surg Am 2003; 85-A Suppl 3: 6774.
  • 36
    Madry H, Cucchiarini M, Stein U, Remberger K, Menger MD, Kohn D, et al. Sustained transgene expression in cartilage defects in vivo after transplantation of articular chondrocytes modified by lipid-mediated gene transfer in a gel suspension delivery system. J Gene Med 2003; 5: 5029.
  • 37
    Wang J, Verdonk P, Elewaut D, Veys Em, Verbruggen G. Homeostasis of the extracellular matrix of normal and osteoarthritic human articular cartilage chondrocytes in vitro. Osteoarthritis Cartilage 2003; 11: 8019.
  • 38
    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 Rheum 2003; 48: 218896.
  • 39
    Von der Mark K, Kirsch T, Nerlich A, Kuss A, Weseloh G, Gluckert K, et al. Type X collagen synthesis in human osteoarthritic cartilage: indication of chondrocyte hypertrophy. Arthritis Rheum 1992; 35: 80611.
  • 40
    Hollander AP, Heathfield TF, Webber C, Iwata Y, Bourne R, Rorabeck C, et al. Increased damage to type II collagen in osteoarthritic articular cartilage detected by a new immunoassay. J Clin Invest 1994; 93: 172232.
  • 41
    Squires GR, Okouneff S, Ionescu M, Poole AR. The pathobiology of focal lesion development in aging human articular cartilage and molecular matrix changes characteristic of osteoarthritis. Arthritis Rheum 2003; 48: 126170.
  • 42
    Sharif M, Whitehouse A, Sharman P, Perry M, Adams M. Increased apoptosis in human osteoarthritic cartilage corresponds to reduced cell density and expression of caspase-3. Arthritis Rheum 2004; 50: 50715.
  • 43
    Tew SR, Li Y, Pothacharoen P, Tweats LM, Hawkins RE, Hardingham TE. Retroviral transduction with SOX9 enhances re-expression of the chondrocyte phenotype in passaged osteoarthritic human articular chondrocytes. Osteoarthritis Cartilage 2005; 13: 809.
  • 44
    Li Y, Tew SR, Russell AM, Gonzalez KR, Hardingham TE, Hawkins AR. Transduction of passaged human articular chondrocytes with adenoviral, retroviral, and lentiviral vectors and the effects of enhanced expression of SOX9. Tissue Eng 2004; 10: 57584.
  • 45
    Doherty PJ, Zhang H, Tremblay L, Manolopoulos V, Marshall KW. Resurfacing of articular cartilage explants with genetically-modified human chondrocytes in vitro. Osteoarthritis Cartilage 1998; 6: 1539.
  • 46
    Kypriotou M, Fossard-Demoor M, Chadjichristos C, Ghayor C, de Crombrugghe B, Pujol JP, et al. SOX9 exerts a bifunctional effect on type II collagen gene (COL2A1) expression in chondrocytes depending on the differentiation state. DNA Cell Biol 2003; 22: 11929.
  • 47
    Rendahl KG, Leff SE, Otten GR, Spratt SK, Bohl D, Van Roey M, et al. Regulation of gene expression in vivo following transduction by two separate rAAV vectors. Nat Biotechnol 1998; 16: 75761.
  • 48
    Trippel SB, Wroblewski J, Makower AM, Whelan MC, Schoenfeld D, Doctrow SR. Regulation of growth-plate chondrocytes by insulin-like growth-factor I and basic fibroblast growth factor. J Bone Joint Surg Am 1993; 75: 17789.
  • 49
    Nixon AJ, Lillich JT, Burton-Wurster N, Lust G, Mohammed HO. Differentiated cellular function in fetal chondrocytes cultured with insulin-like growth factor-I and transforming growth factor-β. J Orthop Res 1998; 16: 53141.