Advertisement

Bone morphogenetic proteins in cartilage biology

  • Susan Chubinskaya
  • Mark Hurtig
  • David C. Rueger
Part of the Progress in Inflammation Research book series (PIR)

Abstract

Cartilage repair and regeneration is a major obstacle in orthopedic medicine. The importance is enormous since osteoarthritis (OA) is a major cause of disability among the adult population in the United States and degenerative disc disease (DDD) is responsible for a significant amount of the chronic back pain. OA is considered a process of attempted, but gradually failing, repair of damaged cartilage extracellular matrix, as the balance between synthesis and breakdown of matrix components is disturbed and shifted towards catabolism. In recent times, members of the bone morphogenetic protein (BMP) family of proteins have demonstrated a great potential as anabolic factors for cartilage repair because of their ability to induce matrix synthesis and promote repair in cartilage.

Keywords

Articular Cartilage Bone Morphogenetic Protein Cartilage Repair Degenerative Disc Disease Matrix Synthesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hogan BLM (1996) Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev 10: 1580–1594Google Scholar
  2. 2.
    Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA (1988) Novel regulators of bone formation: Molecular clones and activities. Science 242: 1528–1534Google Scholar
  3. 3.
    Itoh S, Itoh F, Gourmans M-J, ten Dijke P (2000) Signaling of transforming growth factor-β family members through Smad proteins. Eur J Biochem 267: 6954–6967Google Scholar
  4. 4.
    Massagué J, Chen YG (2000) Controlling TGF-βsignaling. Genes Dev 14: 627–644Google Scholar
  5. 5.
    Roberts AB, Sporn MB (1990) The transforming growth factor-βs. In: Sporn MB, Roberts AB (eds): Peptide growth factors and their receptors, Part I. Springer, Berlin 95, 419–472Google Scholar
  6. 6.
    Goumans MJ, Mummery C (2000) Functional analysis of the TGFβ receptor/Smad pathway through gene ablation in mice. Int J Dev Biol 44: 253–265Google Scholar
  7. 7.
    Schier AF, Shen MM (2000) Nodal signaling in vertebrate development. Nature 403: 385–389Google Scholar
  8. 8.
    Sampath TK, Reddi AH (1981) Dissociative extraction and reconstitution of extracellular matrix components involved in local bone differentiation. Proc Natl Acad Sci USA 78: 7599–7603Google Scholar
  9. 9.
    Urist MR, Mikulski A, Lietze A (1979) Solubilized and insolubilized bone morphogenetic protein. Proc Natl Acad Sci USA 76: 1828–1832Google Scholar
  10. 10.
    Urist MR (1997) Bone morphogenetic protein: The molecularization of skeletal system development. J Bone Miner Res 12: 343–346Google Scholar
  11. 11.
    Chubinskaya S, Kumar B, Merrihew C, Heretis K, Rueger D, and Kuettner KE (2002) Age-related changes in cartilage endogenous BMP-7. Biochim Biophys Acta 1588: 126–134Google Scholar
  12. 12.
    Merrihew C, Kumar B, Heretis K, Rueger DC, Kuettner KE, Chubinskaya S (2003) Alterations in endogenous osteogenic protein-1 (BMP-7) with degeneration of human articular cartilage. J Orthop Res 21: 899–907Google Scholar
  13. 13.
    Soeder S, Hakimiyan A, Rueger D, Kuettner KE, Aigner T, Chubinskaya S (2005) Antisense inhibition of osteogenic protein-1 disturbs human articular cartilage integrity. Arthritis Rheum 52: 468–478Google Scholar
  14. 14.
    Flechtenmacher J, Huch K, Thonar EJ-MA, Mollenhauer JA, Davies SR, Schmid TM, Puhl W, Sampath TK, Aydelotte MB, Kuettner KE (1996) Recombinant human osteogenic protein 1 is a potent stimulator of the synthesis of cartilage proteoglycans and collagens by human articular chondrocytes. Arthritis Rheum 39: 1896–1904Google Scholar
  15. 15.
    Nishida Y, Knudson CB, Eger W, Kuettner KE, Knudson W (2000) Osteogenic protein-1 stimulates cell-associated matrix assembly by normal human articular chondrocytes: Upregulation of hyaluronan synthase, CD 44 and aggrecan. Arthritis Rheum 43: 206–214Google Scholar
  16. 16.
    Loeser RF, Pacione CA, Chubinskaya S (2003) 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 48: 2188–2196Google Scholar
  17. 17.
    Fan Z, Chubinskaya S, Rueger DC, Bau B, Haag J, Aigner T (2004) Regulation of anabolic and catabolic gene expression in normal and osteoarthritic adult human articular chondrocytes by BMP-7 (BMP-7). J Clin Exp Rheum 22: 103–106Google Scholar
  18. 18.
    Loeser R, Chubinskaya S, Pacione C, Im H-J (2005) Basic fibroblast growth factor inhibits the anabolic activity of insulin-like growth factor-1 and osteogenic protein-1 in adult human articular chondrocytes. Arthritis Rheum 52: 3910–3917Google Scholar
  19. 19.
    Chubinskaya S, Hakimiyan A, Pacione C, Yanke A, Rappoport L, Aigner T, Rueger D, Loeser RF (2007) Synergistic Effect of IGF-1 and BMP-7 on matrix formation by normal and OA chondrocytes cultured in alginate beads. Osteoarthritis Cart 15: 421–430Google Scholar
  20. 20.
    Lietman S, Yanagishita M, Sampath TK, Reddi AH (1997) Stimulation of proteoglycan synthesis in explants of porcine articular cartilage by recombinant osteogenic protein-1 (bone morphogenetic protein-7). J Bone Joint Surg 79-A: 1132–1137Google Scholar
  21. 21.
    Nishida Y, Knudson CB, Kuettner KE, Knudson W (2000) Osteogenic protein-1 promotes the synthesis and retention of the extracellular matrix within bovine articular cartilage and chondrocyte cultures. Osteoarthritis Cartilage 8: 127–136Google Scholar
  22. 22.
    Im, HJ, Pacione C, Chubinskaya S, Van Wijnen AJ, Sun Y, and Loeser RF (2003) Inhibitory effects of insulin-like growth factor-1 and osteogenic protein-1 on fibronectin fragment-and interleukin-1beta-stimulated matrix metalloproteinase-13 expression in human chondrocytes. J Biol Chem 278: 25386–25394Google Scholar
  23. 23.
    Chubinskaya S, Hakimiyan A, Otten L, Rappoport L, Rueger DC, Sobhy M, Cole B (2008) Response of human chondrocytes prepared for autologous chondrocyte implantation to growth factors. J Knee Surg (in press)Google Scholar
  24. 24.
    Vukicevic S, Luyten FP, Reddi AH (1989) Stimulation of the expression of osteogenic and chondrogenic phenotypes in vitro by osteogenin. Proc Natl Acad Sci USA 86: 8793–8797Google Scholar
  25. 25.
    Luyten FP, Yu YM, Yanagishita M, Vukicevic S, Hammonds RG, Reddi AH (1992) Natural bovine osteogenin and recombinant human bone morphogenetic protein-2B are equipotent in the maintenance of proteoglycans in bovine articular cartilage explant culture. J Biol Chem 267: 3691–3695Google Scholar
  26. 26.
    Luyten FP, Chen P, Paralkar V, Reddi AH (1994) Recombinant bone morphogenetic protein-4, transforming growth factor-b, and activin A enhance the cartilage phenotype of articular chondrocytes in vitro. Exp Cell Res 210: 224–229Google Scholar
  27. 27.
    Morris E (1996) Differential effects of TGF-beta superfamily members on articular cartilage metabolism: Stimulation by rhBMP-9 and rhBMP-2 and inhibition by TGF-beta. Trans Orthop Res Soc 42: 175Google Scholar
  28. 28.
    van Susante JLC, Buma P, van Beuningen HM, van den Berg WB, Veth RPH (2000) Responsiveness of bovine chondrocytes to growth factors in medium with different serum concentrations. J Orthop Res 18: 68–77Google Scholar
  29. 29.
    Sailor LZ, Hewick RM, Morris EA (1996) Recombinant human bone morphogenetic protein-2 maintains the articular chondrocyte phenotype in long-term culture. J Orthop Res 14: 937–945Google Scholar
  30. 30.
    Stewart MC, Saunders KM, Burton-Wurster N, Macleod JN (2000) Phenotypic stability of articular chondrocytes in vitro: The effect of culture models, bone morphogenetic protein 2, and serum supplementation. J Bone Miner Res 15: 166–174Google Scholar
  31. 31.
    Bobacz K, Gruber R, Soleiman A, Erlacher L, Smolen JS, Graninger WB (2003) Expression of bone morphogenetic protein 6 in healthy and osteoarthritic human articular chondrocytes and stimulation of matrix synthesis in vitro. Arthritis Rheum 48: 2501–1508Google Scholar
  32. 32.
    Chubinskaya S, Rueger DC, Berger RA, Kuettner KE (2002) Osteogenic protein-1 and its receptors in human articular cartilage. In: Hascall V, Kuettner KE (eds): The many faces of osteoarthritis. Birkhäuser, Basel, 81–89Google Scholar
  33. 33.
    Chubinskaya S, Segalite D, Enockson C, Pikovsky D, Gattuso V, Rueger DC (2006) Anabolic response induced by BMPs in human articular chondrocytes: Comparative studies. Proceedings of the 6th ICRS Symposium, San Diego, CA, Jan 8–11Google Scholar
  34. 34.
    Chubinskaya S, Otten L, Soeder S, Aigner T, Loeser RF, Rueger DC (2007) Regulation of anabolic and catabolic pathways by osteogenic protein-1: Gene array data. Trans Orthop Res Soc 53: 546Google Scholar
  35. 35.
    Vinall RL, Lo SH, Reddi AH (2002) Regulation of articular chondrocyte phenotype by bone morphogenetic protein 7, interleukin 1, and cellular context is dependent on the cytoskeleton. Exp Cell Res 272: 32–44Google Scholar
  36. 36.
    Yao J, Cole AA, Huch K, Kuettner KE (1996) The effect of BMP-7 on IL-1beta induced gene expressions of matrix metalloproteinases and TIMP in human articular cartilage. Trans Orthop Res Soc 42: 305Google Scholar
  37. 37.
    Chubinskaya S, Kawakami M, Rapoport L, Matsumoto T, Migita N, Rueger DC (2007) Anti-catabolic effect of BMP-7 in chronically compressed intervertebral discs. J Ortho Res 25: 517–530Google Scholar
  38. 38.
    Hurtig MB, Chubinskaya S (2004) The protective effect of BMP-7 in early traumatic osteoarthritis-animal studies. Trans 5th Combined Orthop Res Soc, Banff, Canada, October 10–13, 70Google Scholar
  39. 39.
    Huser CAM, Peacock M, Davies ME (2006) Inhibition of caspase-9 reduces chondrocyte apoptosis and proteoglycan loss following mechanical trauma. Osteoarthritis Cartilage 14: 1002–1010Google Scholar
  40. 40.
    Huch K, Wilbrink B, Flechtenmacher J, Koepp HE, Aydelotte MB, Sampath TK, Kuettner KE, Mollenhauer JA, Thonar EJ-MA (1997) Effects of recombinant human osteogenic protein 1 on the production of proteoglycan, prostaglandin E2, and interleukin-1 receptor antagonist by human articular chondrocytes cultured in the presence of interleukin-1β. Arthritis Rheum 40: 2157–2161Google Scholar
  41. 41.
    Koepp HE, Sampath KT, Kuettner KE, Homandberg GA (1999) Osteogenic protein-1 (BMP-7) blocks cartilage damage caused by fibronectin fragments and promotes repair by enhancing proteoglycan synthesis. Inflamm Res 47: 1–6Google Scholar
  42. 42.
    Nishida Y, Knudson CB, Knudson W (2004) Osteogenic protein-1 inhibits matrix depletion in a hyaluronan hexasaccharide-induced model of osteoarthritis. Osteoarthritis Cartilage 12: 374–382Google Scholar
  43. 43.
    Fahlgren A, Chubinskaya S, Messner K, Aspenberg P (2006) A capsular incision leads to a fast osteoarthrotic response, but also elevated levels of activated osteogenic protein-1 in rabbit knee joint cartilage. J Scand J Med Sci Sports 16: 456–462Google Scholar
  44. 44.
    Blanco FJ, Geng Y, Lotz M (1995) Differentiation-dependent effects of IL-1 and TGFbeta on human articular chondrocyte proliferation are related to inducible nitric oxide synthase expression. J Immunol 154: 4018–4026Google Scholar
  45. 45.
    Berg WB (2000) Role of nitric oxide in the inhibition of BMP-2-mediated stimulation of proteoglycan synthesis in articular cartilage. Osteoarthritis Cartilage 8: 82–86Google Scholar
  46. 46.
    Elshaier AM, Hakimiyan A, Margulis A, Rueger DC, Chubinskaya S (2005) Effect of IL-1β on BMP-7 signaling in human adult articular chondrocytes. Trans Orthop Res Soc 51: 4Google Scholar
  47. 47.
    Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen BK (1999) Pro-and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol 515: 287–291Google Scholar
  48. 48.
    Beg AA, Finco TS, Nantermet PV, Baldwin AS, Jr (1993) Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of I kappa B alpha: A mechanism for NF-kappa B activation. Mol Cell Biol 13: 3301–3310Google Scholar
  49. 49.
    Lee MJ, Yang CW, Jin DC, Chang YS, Bang BK, Kim YS (2003) Bone morphogenetic protein-7 inhibits constitutive and interleukin-1 beta-induced monocyte chemoattractant protein-1 expression in human mesangial cells: Role for JNK/AP-1 pathway. J Immunol 170: 2557–2563Google Scholar
  50. 50.
    Grimm OH, Gurdon JB (2002) Nuclear exclusion of Smad2 is a mechanism leading to loss of competence. Nat Cell Biol 4: 519–522Google Scholar
  51. 51.
    Kretzschmar M, Doody J, Timokhina I, Massague J (1999) A mechanism of repression of TGFbeta/ Smad signaling by oncogenic Ras. Genes Dev 13: 804–816Google Scholar
  52. 52.
    Bobacz K, Sunk G, Hofstaetter JG, Amoyo L, Toma CD, Akira S, Weichhart T, Saemann M, Smolen JS (2007) Toll-like receptor and chondrocytes: The lipopolysaccharide-induced decrease in cartilage matrix synthesis is dependent on the presence of toll-like receptor 4 and antagonized by bone morphogenetic protein 7. Arthritis Rheum 56: 1880–1893Google Scholar
  53. 53.
    Heldin C-H, Miyazono K, ten Dijke P (1997) TGF-beta signaling from cell membrane to nucleus through SMAD proteins. Nature 390: 465–471Google Scholar
  54. 54.
    Hirota Y, Tsukazaki T, Yonekura A, Miyazaki Y, Osaki M., Shindo H., Yamashita S (2000) Activation of specific MEK-ERK cascade is necessary for TGF-beta signaling and crosstalk with PKA and PKC pathways in cultured rat articular chondrocytes. Osteoarthritis Cartilage 8: 241–247Google Scholar
  55. 55.
    Hu MC, Wasserman D, Hartwig S, Rosenblum ND (2004) p38MAPK acts in the BMP7-dependent stimulatory pathway during epithelial cell morphogenesis and is regulated by Smad1. J Biol Chem 279: 12051–12059Google Scholar
  56. 56.
    Fukui N, Zhu Y, Maloney WJ, Clohisy J, Sandell L (2003) Stimulation of BMP-2 expression by pro-inflammatory cytokines IL-1 and TNF-alpha in normal and osteoarthritic chondrocytes. J Bone Joint Surg Am 85-A (Suppl 3): 59–66Google Scholar
  57. 57.
    Chen AL, Fang C, Liu C, Leslie MP, Chang E, Di Cesare PE (2004) Expression of bone morphogenetic proteins, receptors, and tissue inhibitors in human fetal, adult, and osteoarthritic articular cartilage. J Orthop Res 22: 1188–1192Google Scholar
  58. 58.
    Erlacher L, Ng C-K, Ullrich R, Krieger S, Luyten FP (1998) Presence of cartilage-derived morphogenetic proteins in articular cartilage and enhancement of matrix replacement in vitro. Arthritis Rheum 41: 263–273Google Scholar
  59. 59.
    Cui Y, Jean F, Thomas G, Christian JL (1998) BMP-4 is proteolytically activated by furin and/or PC6 during vertebral embryonic development. EMBO J 17: 4735–4743Google Scholar
  60. 60.
    Chubinskaya S, Oakes B, Shimmin A, Rueger DC, Kildey R (2004) Anabolic response in the articular joint induced by BMP-7 in the goat model of osteochondral defects. Proceedings of the 5th ICRS Symposium, Gent, Belgium, May 26–29, 365Google Scholar
  61. 61.
    Anderson HC, Hodges PT, Aguilera XM, Missana L, Moylan PE (2000) Bone morphogenetic protein (BMP) localization in developing human and rat growth plate, metaphysis, epiphysis, and articular cartilage. J Histochem Cytochem 48: 1493–1502Google Scholar
  62. 62.
    Rueger DC, Chubinskaya S (2004) BMPs in articular cartilage repair. In: Vukicevic S, Sampath KT (eds): Bone morphogenetic proteins: Regeneration of bone and beyond. Birkhäuser, Basel, 109–132Google Scholar
  63. 63.
    Chubinskaya S, Frank BS, Michalska M, Kumar B, Merrihew CA, Thonar EJ-MA, Lenz ME, Otten L, Rueger DC, Block JA (2006) Osteoarthritic protein-1 in synovial fluid from patients with rheumatoid arthritis or osteoarthritis: Relationship to disease and levels of hyaluronan and antigenic keratan sulfate. Arthritis Res Ther 8: R73Google Scholar
  64. 64.
    Miossec R, Naviliat M, Dupuy DA, Sany J, Banchereau J (1990) Low levels of interleukin-4 and high levels of transforming growth factor beta in rheumatoid synovitis. Arthritis Rheum 33: 1180–1187Google Scholar
  65. 65.
    Taketazu F, Kato M, Gobl A, Iichijo H, ten Dijke P, Itoh J, Kyogoku M, Ronnelid J, Miyazono K, Heldin CH (1994) Enhanced expression of transforming growth factorbeta s and transforming growth factor-beta type II receptor in the synovial tissues of patients with rheumatoid arthritis. Lab Invest 70: 620–630Google Scholar
  66. 66.
    Muehleman C, Kuettner KE, Rueger DC, ten Dijke P, Chubinskaya S (2002) Immunohistochemical localization of osteogenic protein-1 and its receptors in rabbit articular cartilage. J Histochem Cytochem 50: 1341–1350Google Scholar
  67. 67.
    Patwari P, Chubinskaya S, Hakimiyan A, Kumar B, Cole AA, Kuettner KE, Rueger DC, Grodzinsky AJ (2003) Injurious compression of adult human donor cartilage explants: Investigation of anabolic and catabolic processes. Trans Orthop Res Soc 49: 695Google Scholar
  68. 68.
    Chu CQ, Field M, Allard S, Abney E, Feldman M, Maini RN (1992) Detection of cytokines at the cartilage/pannus junction in patients with rheumatoid arthritis: Implication for the role of cytokines in cartilage destruction and repair. Br J Rheumatol 31: 653–661Google Scholar
  69. 69.
    Fava R, Olsen N, Keski Oja J, Moses H, Pincus T (1989) Active and latent forms of transforming growth factor beta activity in synovial effusions. J Exp Med 169: 291–296Google Scholar
  70. 70.
    Sellers RS, Peluso D, Morris EA (1997) The effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the healing of full-thickness defects of articular cartilage. J Bone Joint Surg Am 79-A: 1542–1463Google Scholar
  71. 71.
    Sellers RC, Zhang R, Glasson SS, Kim HD, Peluso D, D’Augusta DA, Beckwith K, Morris EA (2000) Repair of articular cartilage defects one year after treatment with recombinant human bone morphogenetic protein-2 (rhBMP-2). J Bone Joint Surg Am 82-A: 151–160Google Scholar
  72. 72.
    Frenkel SR, Saadeh PB, Mehrar BJ, Chin GS, Steinbrech DS, Brent B, Gittes JK, Longaker MT (2000) Transforming growth factor beta superfamily members: Role in cartilage modeling. Plast Recon Surg 105: 980–990Google Scholar
  73. 73.
    Cook SD, Rueger DC (1996) Osteogenic protein-1: Biology and applications. Clin Orthop Relat Res 324: 29–38Google Scholar
  74. 74.
    Grgic M, Jelic M, Basic V, Basic N, Pecina M, Vukicevic S (1997) Regeneration of articular cartilage defects in rabbits by osteogenic protein-1 (bone morphogenetic protein-7). Acta Med Croatia 51: 23–27Google Scholar
  75. 75.
    Mattioli-Belmonte M, Gigante A, Muzzarelli RAA, Politano R, De Benedittis A, Specchia N, Buffa A, Biagini G, Greco F (1999) N,N-Dicarboxymethyl chitosan as delivery agent for bone morphogenetic protein in the repair of articular cartilage. Med Biol Eng Comp 37: 130–134Google Scholar
  76. 76.
    Simank HG, Sergi C, Jung M, Adolf S, Eckhardt C, Ehemann V, Ries R, Lill C, Richter W (2004) Effects of local application of growth and differentiation factor-5 (GDF-5) in a full-thickness cartilage defect model. Growth Factors 22: 35–43Google Scholar
  77. 77.
    Mason JM, Breibart AS, Barcia M, Porti D, Pergolizzi RG, Grande DA (2000) Cartilage and bone regeneration using gene-enhanced tissue engineering. Clin Orthop Relat Res (379S): S171–S178Google Scholar
  78. 78.
    Katayama R, Wakitani S, Tsumaki N, Morita Y, Matsushita I, Gejo R, Kimura T (2004) Repair of articular cartilage defects in rabbits using CDMP1 gene-transfected autologous mesenchymal cells derived from bone marrow. Rheumatology (Oxford) 43: 980–985Google Scholar
  79. 79.
    Di Cesare PE, Frenkel SR, Carlson CS, Fang C, Liu C (2006) Regional gene therapy for full-thickness articular cartilage lesions using naked DNA with a collagen matrix. J Orthop Res 24: 1118–1127Google Scholar
  80. 80.
    Cook SD, Patron LP, Salkeld SL, Rueger DC (2003) Repair of articular cartilage defects with osteogenic protein-1 (BMP-7) in dogs. J Bone Joint Surg 85-A(Supp 3): 116–123Google Scholar
  81. 81.
    Louwerse RT, Iheyligers IC, Klein-Nulend J, Sugiihara S, van Kampen GPJ, Semeins CM, Goei SW, de Koning MHMT, Wuisman PIJM, Burger EH (2000) Use of recombinant human osteogenic protein-1 for the repair of subchondral defects in articular cartilage in goats. J Biomed Mater Res 49: 506–516Google Scholar
  82. 82.
    Hunziker EB, Driesang MK (2003) Functional barrier principle for growth-factor-based articular cartilage repair. Osteoarthritis Cartilage 11: 320–327Google Scholar
  83. 83.
    Jung M, Tuischer JS, Sergi C, Gotterbarm T, Pohl J, Richter W, Simank HG (2006) Local application of a collagen type I/hyaluronate matrix and growth and differentiation factor 5 influences the closure of osteochondral defects in a minipig model by enchondral ossification. Growth Factors 24: 225–232Google Scholar
  84. 84.
    Shimmin A, Young D, O’Leary S, Shih MS, Rueger DC Walsh WR (2002) Growth factor augmentation of an ovine mosaicplasty model. Proceedings of the 4th ICRS Symposium, Toronto, Canada, June 15–18, 16Google Scholar
  85. 85.
    Jelic M, Pecina M, Haspl M, Kos J, Taylor K, Maticic D, McCartney J, Yin S, Rueger D, Vukicevic S (2001) Regeneration of articular cartilage chondral defects by osteogenic protein-1 (bone morphogenetic protein-7) in sheep. Growth Factors 19: 101–113Google Scholar
  86. 86.
    Hunziker EB, Dreisang IMK, Morris EA (2001) Chondrogenesis in cartilage repair is induced by members of the transforming growth factor-beta superfamily. Clin Orthop Relat Res (391S): S171–S181Google Scholar
  87. 87.
    Kuo AC, Rodrigo JJ, Reddi AH, Curtiss S, Grotkopp E, Chiu M (2006) Microfracture and bone morphogenetic protein 7 (BMP-7) synergistically stimulate articular cartilage repair. Osteoarthritis Cartilage 14: 1126–1135Google Scholar
  88. 88.
    Hidaka C, Goodrich LR, Chen CT, Warren RF, Crystal RG, Nixon AJ (2003) Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7. J Orthop Res 21: 573–583Google Scholar
  89. 89.
    Park J, Gelse K, Frank S, von der Mark K, Aigner T, Schneider H (2006) Transgeneactivated mesenchymal cells for articular cartilage repair: A comparison of primary bone marrow-, perichondrium/periosteum-and fat-derived cells. J Gene Med 8: 112–125Google Scholar
  90. 90.
    Colwell CW Jr, D’Lima DD, Hoenecke HR, Fronek J, Pulido P, Morris BA, Chung C, Resnick D, Lotz M (2001) In vivo changes after mechanical injury. Clin Orthop Relat Res 391Suppl: S116–123Google Scholar
  91. 91.
    Kim HD, Valentini RF (2002) Retention and activity of BMP-2 in hyaluronic acid-based scaffolds in vitro. J Biomed Mater Res 59: 573–578Google Scholar
  92. 92.
    Sugimori K, Matsui K, Motomura H, Tokoro T, Wang J, Higa S, Kimura T, Kitajima I (2005) BMP-2 prevents apoptosis of the N1511 chondrocytic cell line through PI3K/ Akt-mediated NF-kappa B activation. J Bone Miner Metab 23: 411–419Google Scholar
  93. 93.
    Hurtig MB (2006) Delayed administration of BMP-7 reduces articular degeneration after contusive impact injury. Trans Orthop Res Soc 52: 1338Google Scholar
  94. 94.
    Kaps C, Bramlage C, Smolian H, Haisch A, Ungethum U, Burmester GR, Sittinger M, Gross G, Haupl T (2002) Bone morphogenetic proteins promote cartilage differentiation and protect engineered artificial cartilage from fibroblast invasion and destruction. Arthritis Rheum 46: 149–162Google Scholar
  95. 95.
    Costa-Paz M, Muscolo DL, Ayerza M, Makino A, Aponte-Tinao L (2001) Magnetic resonance imaging follow-up study of bone bruises associated with anterior cruciate ligament ruptures. Arthroscopy 17: 445–449Google Scholar
  96. 96.
    Cook SD, Barrack RL, Patron LP, Sakeld SL (2004) Osteogenic protein-1 in knee arthritis and arthroplasty. Clin Orthop Relat Res 428: 140–145Google Scholar
  97. 97.
    Badlani N, Inoue A, Healey R, Coutts R, Amiel D (2007) The protective effect of BMP-7 on articular cartilage in the development of osteoarthritis. Proceedings of the 7th ICRS Symposium, Warsaw, Sept 29–Oct 2, 150Google Scholar
  98. 98.
    Bolam C, Hurtig M, Cruz A, McEwen B (2006) Characterization of a model of posttraumatic osteoarthritis in the equine femorotibial joint. Am J Vet Res 67: 433–447Google Scholar
  99. 99.
    Hurtig M, Akens M (2004) A comparison of the contusive impact and ACL transection models of osteoarthritis. Trans Orthop Res Soc 50: 927Google Scholar
  100. 100.
    Hurtig MB, Runciman J, Dickey J, Newbound G (2002) A standardized model of knee injury. Trans Orthop Res Soc 48: 104Google Scholar
  101. 101.
    Gartlehner G, Hansen RA, Jonas BL, Thieda P, Lohr KN (2006) The comparative efficacy and safety of biologics for the treatment of rheumatoid arthritis: A systematic review and metaanalysis. J Rheumatol 33: 2398–2408Google Scholar
  102. 102.
    Masuda K, Takegami K, An H, Kumano F, Chiba K, Andersson GBJ, Schmid T, Thonar, E (2003) Recombinant osteogenic protein-1 upregulates extracellular matrix metabolism by rabbit annulus fibrosus and nucleus pulposus cells cultured in alginate beads. J Orthop Res 21: 922–930Google Scholar
  103. 103.
    Zhang Y, An HS, Song S, Toofanfard M, Masuda K, Andersson GB, Thonar EJ (2004) Growth factor osteogenic protein-1: Differing effects on cells from three distinct zones in the bovine intervertebral disc. Am J Phys Med Rehabil 83: 515–521Google Scholar
  104. 104.
    Chujo T, An HS, Akeda K, Miyamoto K, Muehleman C, Attawia M, Andersson G, Masuda K (2006) Effects of growth differentiation factor-5 on the intervertebral disc — In vitro bovine study and in vivo rabbit disc degeneration model study. Spine 31: 2909–2917Google Scholar
  105. 105.
    Takegami K, An HS, Kumano F, Chiba K, Thonar EJ, Singh K, Masuda K (2005) Osteogenic protein-1 is most effective in stimulating nucleus pulposus and annulus fibrosus cells to repair their matrix after chondroitinase ABC-induced in vitro chemonucleolysis. Spine J 5: 231–238Google Scholar
  106. 106.
    Takegami K, Thonar EJMA, An HS, Kamada H, Masuda K (2002) Osteogenic protein-1 enhances matrix replenishment by intervertebral disc cells previously exposed to interleukin-1. Spine 27: 1318–1325Google Scholar
  107. 107.
    An HS, Takegami K, Kamada H, Nguyen CM, Thonar E, Singh K, Andersson GB, Masuda K (2005) Intradiscal administration of Osteogenic Protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits. Spine 30: 25–32Google Scholar
  108. 108.
    Masuda K, Imai Y, Okuma M, Muehleman C, Nakagawa K, Akeda K, Thonar E, Andersson G, An HS (2006) Osteogenic protein-1 injection into a degenerated disc induces the restoration of disc height and structural changes in the rabbit anular puncture model. Spine 31: 742–754Google Scholar
  109. 109.
    Miyamoto K, Masuda K, Kim JG, Inoue N, Akeda K, Andersson GB, An HS (2007) Intradiscal injections of osteogenic protein-1 restore the viscoelastic properties of degenerated intervertebral discs. Spine J 6: 692–703Google Scholar
  110. 110.
    Imai Y, Okuma M, An HS, Nakagawa K, Yamada M, Muehleman C, Thonar E, Masuda K (2007) Restoration of disc height loss by recombinant human osteogenic protein-1 injection into intervertebral discs undergoing degeneration induced by an intradiscal injection of chondroitinase ABC. Spine 32: 1197–1205Google Scholar
  111. 111.
    Walsh AJ, Bradford DS, Lotz JC (2004) In vivo growth factor treatment of degenerated intervertebral discs. Spine 29: 156–163Google Scholar
  112. 112.
    Kawakami M, Matsumoto T, Hashizume H, Kuribayashi K, Chubinskaya S, Yoshida M (2005) Osteogenic protein-1 (osteogenic protein-1/bone morphogenetic protein-7) inhibits degeneration and pain-related behavior induced by chronically compressed nucleus pulposus in the rat. Spine 30: 1933–1939Google Scholar
  113. 113.
    Wallach CJ, Kim JS, Sobajima S, Lattermann C, Oxner WM, McFadden K, Robbins PD, Gilbertson LG, Kang JD (2006) Safety assessment of intradiscal gene transfer: A pilot study. Spine J 6: 107–112Google Scholar
  114. 114.
    Katic V, Majstorovic L, Maticic D, Pirkic B, Yin S, Kos J, Martinovic S, McCartney JE, Vukicevic S (2000) Biological repair of thyroid cartilage defects by osteogenic protein-1 (bone morphogenetic protein-7) in dog. Growth Factors 17: 221–232Google Scholar
  115. 115.
    Okamoto T, Yamamoto Y, Gotoh M, Huang CL, Nakamura T, Shimizu Y, Tabata Y, Yokomise H (2004) Slow release of bone morphogenetic protein 2 from a gelatin sponge to promote regeneration of tracheal cartilage in a canine model. J Thorac Cardiovasc Surg 127: 329–334Google Scholar
  116. 116.
    Tcacencu I, Carlsöö B, Stierna P, Hultenby K (2006) Local treatment of cricoid cartilage defects with rhBMP-2 induces growth plate-like morphology of chondrogenesis. Otolaryngol Head Neck Surg 135: 427–433Google Scholar
  117. 117.
    Hicks DL, Sage AB, Shelton E, Schumacher BL, Sah RL, Watson D (2007) Effect of bone morphogenetic proteins 2 and 7 on septal chondrocytes in alginate. Otolaryngol Head Neck Surg 136: 373–379Google Scholar
  118. 118.
    Lietman SA, Hobbs W, Inoue N, Reddi AH (2003) Effects of selected growth factors on porcine meniscus in chemically defined medium. Orthopedics 26: 799–803Google Scholar
  119. 119.
    van Beuningen HM, Glansbeek HL, van der Kraan PM, van den Berg W (1998) Differential effects of local application of BMP-2 or TGF-β1 on both articular cartilage composition and osteophyte formation. Osteoarthritis Cartilage 6: 306–317Google Scholar
  120. 120.
    Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P, Gunther K, Hauselmann H, Herrero-Beaumont G, Kaklamanis P 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: 1145–1155Google Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2008

Authors and Affiliations

  • Susan Chubinskaya
    • 1
  • Mark Hurtig
    • 2
  • David C. Rueger
    • 3
  1. 1.Department of BiochemistryRush University Medical CenterChicagoUSA
  2. 2.Guelph UniversityGuelphCanada
  3. 3.Stryker Biotech DivisionHopkintonUSA

Personalised recommendations