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Potential roles of bone morphogenetic proteins (BMPs) in skeletal repair and regeneration

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References

  1. MR Urist (1965) ArticleTitleBone: formation by autoinduction Science 150 893–899 Occurrence Handle5319761 Occurrence Handle1:STN:280:DyaF28%2FhvFekuw%3D%3D Occurrence Handle10.1126/science.150.3698.893

    Article  PubMed  CAS  Google Scholar 

  2. MR Urist BS Strates (1971) ArticleTitleBone morphogenetic protein J Dent Res 50 1392–1406 Occurrence Handle4943222 Occurrence Handle1:CAS:528:DyaE38Xotl2gsw%3D%3D

    PubMed  CAS  Google Scholar 

  3. JM Wozney V Rosen AJ Celeste LM Mitsock MJ Whitters RW Kriz RM Hewick EA Wang (1988) ArticleTitleNovel regulators of bone formation: molecular clones and activities Science 242 1528–1534 Occurrence Handle3201241 Occurrence Handle1:CAS:528:DyaL1MXkvFantr8%3D Occurrence Handle10.1126/science.3201241

    Article  PubMed  CAS  Google Scholar 

  4. K Takaoka H Yoshikawa J Hashimoto S Miyamoto K Masuhara H Nakahara M Matsui K Ono (1993) ArticleTitlePurification and characterization of a bone-inducing protein from a murine osteosarcoma (Dunn type) Clin Orthop 292 329–336 Occurrence Handle8519128

    PubMed  Google Scholar 

  5. K Takaoka H Yoshikawa J Hasimoto K Masuhara S Miyamoto S Suzuki K Ono M Matsui S Oikawa N Tsuruoka Y Tawaragi C Inuzuka T Kitayama M Sugiyama M Tsujimoto T Nakanishi H Nakazato (1993) ArticleTitleGene cloning and expression of a bone morphogenetic protein derived from a murine osteosarcoma Clin Orthop 294 344–352 Occurrence Handle8358941

    PubMed  Google Scholar 

  6. AH Reddi (2005) ArticleTitleBMPs: from bone morphogenetic proteins to body morphogenetic proteins Cytokine Growth Factor Rev 16 249–250 Occurrence Handle15949967 Occurrence Handle1:CAS:528:DC%2BD2MXlsl2rtLw%3D Occurrence Handle10.1016/j.cytogfr.2005.04.003

    Article  PubMed  CAS  Google Scholar 

  7. P ten Dijke H Yamashita TK Sampath AH Reddi M Estevez DL Riddle H Ichijo CH Heldin K Miyazono (1994) ArticleTitleIdentification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4 J Biol Chem 269 16985–16988 Occurrence Handle8006002 Occurrence Handle1:CAS:528:DyaK2cXltVSmurc%3D

    PubMed  CAS  Google Scholar 

  8. BL Rosenzweig T Imamura T Okadome GN Cox H Yamashita DP ten CH Heldin K Miyazono (1995) ArticleTitleCloning and characterization of a human type II receptor for bone morphogenetic proteins Proc Natl Acad Sci U S A 92 7632–7636 Occurrence Handle7644468 Occurrence Handle1:STN:280:DyaK2Mznt1egtg%3D%3D Occurrence Handle10.1073/pnas.92.17.7632

    Article  PubMed  CAS  Google Scholar 

  9. H Zou R Wieser J Massague L Niswander (1997) ArticleTitleDistinct roles of type I bone morphogenetic protein receptors in the formation and differentiation of cartilage Genes Dev 11 2191–2203 Occurrence Handle9303535 Occurrence Handle1:CAS:528:DyaK2sXmtVertbc%3D

    PubMed  CAS  Google Scholar 

  10. CH Heldin K Miyazono P ten Dijke (1997) ArticleTitleTGF-beta signalling from cell membrane to nucleus through SMAD proteins Nature 390 465–471 Occurrence Handle9393997 Occurrence Handle1:CAS:528:DyaK2sXnvFyrtLo%3D Occurrence Handle10.1038/37284

    Article  PubMed  CAS  Google Scholar 

  11. N Tsumaki K Tanaka E Arikawa-Hirasawa T Nakase T Kimura JT Thomas T Ochi FP Luyten Y Yamada (1999) ArticleTitleRole of CDMP-1 in skeletal morphogenesis: promotion of mesenchymal cell recruitment and chondrocyte differentiation J Cell Biol 144 161–173 Occurrence Handle9885252 Occurrence Handle1:CAS:528:DyaK1MXjs1yhuw%3D%3D Occurrence Handle10.1083/jcb.144.1.161

    Article  PubMed  CAS  Google Scholar 

  12. NM Wolfman G Hattersley K Cox AJ Celeste R Nelson N Yamaji JL Dube E DiBlasio-Smith J Nove JJ Song JM Wozney V Rosen (1997) ArticleTitleEctopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family J Clin Invest 100 321–330 Occurrence Handle9218508 Occurrence Handle1:CAS:528:DyaK2sXkslKns7Y%3D Occurrence Handle10.1172/JCI119537

    Article  PubMed  CAS  Google Scholar 

  13. GE Friedlaender CR Perry JD Cole SD Cook G Cierny GF Muschler GA Zych JH Calhoun AJ LaForte S Yin (2001) ArticleTitleOsteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions J Bone Joint Surg Am 83-A IssueIDSuppl 1 S151–158 Occurrence Handle11314793

    PubMed  Google Scholar 

  14. S Govender C Csimma HK Genant A Valentin-Opran Y Amit et al. (2002) ArticleTitleRecombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of 450 patients J Bone Joint Surg Am 84-A 2123–2134 Occurrence Handle12473698

    PubMed  Google Scholar 

  15. T Nakase S Nomura H Yoshikawa J Hashimoto S Hirota Y Kitamura S Oikawa K Ono K Takaoka (1994) ArticleTitleTransient and localized expression of bone morphogenetic protein 4 messenger RNA during fracture healing J Bone Miner Res 9 651–659 Occurrence Handle8053394 Occurrence Handle1:CAS:528:DyaK2cXktVKmtrg%3D

    PubMed  CAS  Google Scholar 

  16. T Nakase K Takaoka S Mizuo S Hirota M Sato H Yoshikawa S Nomura (1996) ArticleTitleExpression of bone morphogenetic protein-4 mRNA during the process of bone formation in embryogenesis and fracture repair Wound Repair and Regeneration (Wound Rep Reg) 4 82–86 Occurrence Handle10.1046/j.1524-475X.1996.40114.x Occurrence Handle1:STN:280:DC%2BD28nptlClsA%3D%3D

    Article  CAS  Google Scholar 

  17. T Onishi Y Ishidou T Nagamine K Yone T Imamura M Kato TK Sampath P ten Dijke T Sakou (1998) ArticleTitleDistinct and overlapping patterns of localization of bone morphogenetic protein (BMP) family members and a BMP type II receptor during fracture healing in rats Bone 22 605–612 Occurrence Handle9626398 Occurrence Handle1:CAS:528:DyaK1cXjvVeltLs%3D Occurrence Handle10.1016/S8756-3282(98)00056-8

    Article  PubMed  CAS  Google Scholar 

  18. MP Bostrom JM Lane WS Berberian AA Missri E Tomin A Weiland SB Doty D Glaser VM Rosen (1995) ArticleTitleImmunolocalization and expression of bone morphogenetic proteins 2 and 4 in fracture healing J Orthop Res 13 357–367 Occurrence Handle7602397 Occurrence Handle1:STN:280:DyaK2MzisF2gsw%3D%3D Occurrence Handle10.1002/jor.1100130309

    Article  PubMed  CAS  Google Scholar 

  19. RA Meyer SuffixJr MH Meyer M Tenholder S Wondracek R Wasserman P Garges (2003) ArticleTitleGene expression in older rats with delayed union of femoral fractures J Bone Joint Surg Am 85-A 1243–1254 Occurrence Handle12851349

    PubMed  Google Scholar 

  20. Y Ishidou I Kitajima H Obama I Maruyama F Murata T Imamura N Yamada P ten Dijke K Miyazono T Sakou (1995) ArticleTitleEnhanced expression of type I receptors for bone morphogenetic proteins during bone formation J Bone Miner Res 10 1651–1659 Occurrence Handle8592941 Occurrence Handle1:CAS:528:DyaK28XhslSqsw%3D%3D Occurrence Handle10.1002/jbmr.5650101107

    Article  PubMed  CAS  Google Scholar 

  21. CH Rundle N Miyakoshi Y Kasukawa ST Chen MH Sheng JE Wergedal KH Lau DJ Baylink (2003) ArticleTitleIn vivo bone formation in fracture repair induced by direct retroviral-based gene therapy with bone morphogenetic protein-4 Bone 32 591–601 Occurrence Handle12810166 Occurrence Handle1:CAS:528:DC%2BD3sXks1WksL4%3D Occurrence Handle10.1016/S8756-3282(03)00096-6

    Article  PubMed  CAS  Google Scholar 

  22. S Spinella-Jaegle G Rawadi S Kawai S Gallea C Faucheu P Mollat B Courtois B Bergaud V Ramez AM Blanchet G Adelmant R Baron S Roman-Roman (2001) ArticleTitleSonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation J Cell Sci 114 2085–2094 Occurrence Handle11493644 Occurrence Handle1:CAS:528:DC%2BD3MXkslWktbw%3D

    PubMed  CAS  Google Scholar 

  23. LC Murtaugh JH Chyung AB Lassar (1999) ArticleTitleSonic hedgehog promotes somitic chondrogenesis by altering the cellular response to BMP signaling Genes Dev 13 225–237 Occurrence Handle9925646 Occurrence Handle1:CAS:528:DyaK1MXhtVOksbc%3D

    PubMed  CAS  Google Scholar 

  24. T Miyaji T Nakase M Iwasaki K Kuriyama N Tamai C Higuchi A Myoui T Tomita H Yoshikawa (2003) ArticleTitleExpression and distribution of transcripts for sonic hedgehog in the early phase of fracture repair Histochem Cell Biol 119 233–237 Occurrence Handle12649738 Occurrence Handle1:CAS:528:DC%2BD3sXit1KitLg%3D

    PubMed  CAS  Google Scholar 

  25. Y Imai H Terai C Nomura-Furuwatari S Mizuno K Matsumoto T Nakamura K Takaoka (2005) ArticleTitleHepatocyte growth factor contributes to fracture repair by upregulating the expression of BMP receptors J Bone Miner Res 20 1723–1730 Occurrence Handle16160730 Occurrence Handle1:CAS:528:DC%2BD2MXhtFGrtLjJ Occurrence Handle10.1359/JBMR.050607

    Article  PubMed  CAS  Google Scholar 

  26. Y Yoshimura S Nomura S Kawasaki T Tsutsumimoto T Shimizu K Takaoka (2001) ArticleTitleColocalization of noggin and bone morphogenetic protein-4 during fracture healing J Bone Miner Res 16 876–884 Occurrence Handle11341332 Occurrence Handle1:CAS:528:DC%2BD3MXjs1Wjur4%3D Occurrence Handle10.1359/jbmr.2001.16.5.876

    Article  PubMed  CAS  Google Scholar 

  27. N Tsumaki T Nakase T Miyaji M Kakiuchi T Kimura T Ochi H Yoshikawa (2002) ArticleTitleBone morphogenetic protein signals are required for cartilage formation and differently regulate joint development during skeletogenesis J Bone Miner Res 17 898–906 Occurrence Handle12009021 Occurrence Handle1:CAS:528:DC%2BD38XktVSktrc%3D Occurrence Handle10.1359/jbmr.2002.17.5.898

    Article  PubMed  CAS  Google Scholar 

  28. P Kloen SB Doty E Gordon IF Rubel MJ Goumans DL Helfet (2002) ArticleTitleExpression and activation of the BMP-signaling components in human fracture nonunions J Bone Joint Surg Am 84-A 1909–1918 Occurrence Handle12429748

    PubMed  Google Scholar 

  29. P Kloen M Di Paola O Borens J Richmond G Perino DL Helfet MJ Goumans (2003) ArticleTitleBMP signaling components are expressed in human fracture callus Bone 33 362–371 Occurrence Handle13678778 Occurrence Handle1:CAS:528:DC%2BD3sXnt1GlsLY%3D Occurrence Handle10.1016/S8756-3282(03)00191-1

    Article  PubMed  CAS  Google Scholar 

  30. T Nakase K Sugamoto T Miyamoto N Tsumaki FP Luyten H Inui A Myoui T Tomita H Yoshikawa (2002) ArticleTitleActivation of cartilage-derived morphogenetic protein-1 in torn rotator cuff Clin Orthop 399 140–145 Occurrence Handle12011702

    PubMed  Google Scholar 

  31. B Mikic BJ Schalet RT Clark V Gaschen EB Hunziker (2001) ArticleTitleGDF-5 deficiency in mice alters the ultrastructure, mechanical properties and composition of the Achilles tendon J Orthop Res 19 365–371 Occurrence Handle11398847 Occurrence Handle1:CAS:528:DC%2BD3MXltVGht70%3D Occurrence Handle10.1016/S0736-0266(00)90018-4

    Article  PubMed  CAS  Google Scholar 

  32. A Chhabra D Tsou RT Clark V Gaschen EB Hunziker B Mikic (2003) ArticleTitleGDF-5 deficiency in mice delays Achilles tendon healing J Orthop Res 21 826–835 Occurrence Handle12919870 Occurrence Handle1:CAS:528:DC%2BD3sXmt1WktLk%3D Occurrence Handle10.1016/S0736-0266(03)00049-4

    Article  PubMed  CAS  Google Scholar 

  33. P Aspenberg C Forslund (1999) ArticleTitleEnhanced tendon healing with GDF 5 and 6 Acta Orthop Scand 70 51–54 Occurrence Handle10191749 Occurrence Handle1:STN:280:DyaK1M3gslCksQ%3D%3D Occurrence Handle10.3109/17453679909000958

    Article  PubMed  CAS  Google Scholar 

  34. GA Ilizarov (1990) ArticleTitleClinical application of the tension-stress effect for limb lengthening Clin Orthop 250 8–26 Occurrence Handle2403497

    PubMed  Google Scholar 

  35. M Sato T Ochi T Nakase S Hirota Y Kitamura S Nomura N Yasui (1999) ArticleTitleMechanical tension-stress induces expression of bone morphogenetic protein (BMP)-2 and BMP-4, but not BMP-6, BMP-7, and GDF-5 mRNA, during distraction osteogenesis J Bone Miner Res 14 1084–1095 Occurrence Handle10404008 Occurrence Handle1:CAS:528:DyaK1MXkvVyjsLw%3D Occurrence Handle10.1359/jbmr.1999.14.7.1084

    Article  PubMed  CAS  Google Scholar 

  36. WF Lestini SW Wiesel (1989) ArticleTitleThe pathogenesis of cervical spondylosis Clin Orthop 239 69–93 Occurrence Handle2536306

    PubMed  Google Scholar 

  37. S Miyamoto K Yonenobu K Ono (1991) ArticleTitleExperimental cervical spondylosis in the mouse Spine 16 S495–500 Occurrence Handle1801260 Occurrence Handle1:STN:280:DyaK387ps1KltQ%3D%3D Occurrence Handle10.1097/00007632-199110001-00008

    Article  PubMed  CAS  Google Scholar 

  38. T Nakase K Ariga S Miyamoto S Okuda T Tomita M Iwasaki K Yonenobu H Yoshikawa (2001) ArticleTitleDistribution of genes for bone morphogenetic protein-4, -6, growth differentiation factor-5, and bone morphogenetic protein receptors in the process of experimental spondylosis in mice J Neurosurg Spine 94 68–75 Occurrence Handle1:CAS:528:DC%2BD3MXls1CrtA%3D%3D Occurrence Handle10.3171/spi.2001.94.1.0068

    Article  CAS  Google Scholar 

  39. J Inamasu BH Guiot DC Sachs (2006) ArticleTitleOssification of the posterior longitudinal ligament: an update on its biology, epidemiology, and natural history Neurosurgery 58 1027–1039 Occurrence Handle16723881 Occurrence Handle10.1227/01.NEU.0000215867.87770.73

    Article  PubMed  Google Scholar 

  40. K Hayashi Y Ishidou K Yonemori T Nagamine N Origuchi S Maeda T Imamura M Kato H Yoshida TK Sampath P ten Dijke T Sakou (1997) ArticleTitleExpression and localization of bone morphogenetic proteins (BMPs) and BMP receptors in ossification of the ligamentum flavum Bone 21 23–30 Occurrence Handle9213004 Occurrence Handle1:CAS:528:DyaK2sXkslamsLY%3D Occurrence Handle10.1016/S8756-3282(97)00080-X

    Article  PubMed  CAS  Google Scholar 

  41. H Kawaguchi T Kurokawa Y Hoshino H Kawahara E Ogata T Matsumoto (1992) ArticleTitleImmunohistochemical demonstration of bone morphogenetic protein-2 and transforming growth factor-beta in the ossification of the posterior longitudinal ligament of the cervical spine Spine 17 S33–36 Occurrence Handle1566182 Occurrence Handle1:STN:280:DyaK383ivFGqtw%3D%3D Occurrence Handle10.1097/00007632-199203001-00007

    Article  PubMed  CAS  Google Scholar 

  42. M Ono WJ Russell S Kudo Y Kuroiwa M Takamori S Motomura J Murakami (1982) ArticleTitleOssification of the thoracic posterior longitudinal ligament in a fixed population. Radiological and neurological manifestations Radiology 143 469–474 Occurrence Handle7071349 Occurrence Handle1:STN:280:DyaL387nsFeitg%3D%3D

    PubMed  CAS  Google Scholar 

  43. T Yanagi (1997) Clinical manifestation of thoracic ossification of the posterior longitudinal ligament and ossification of the yellow ligament K Yonenobu T Sakou K Ono (Eds) OPLL: Ossification of the Posterior Longitudinal Ligament Springer-Verlag Tokyo 95–98

    Google Scholar 

  44. T Nakase K Ariga K Yonenobu N Tsumaki F Luyten Y Mukai I Sato H Yoshikawa (2001) ArticleTitleActivation and localization of cartilage-derived morphogenetic protein-1 at the site of ossification of the ligamentum flavum Eur Spine J 10 289–294 Occurrence Handle11563613 Occurrence Handle1:STN:280:DC%2BD3Mrhs1eqtA%3D%3D Occurrence Handle10.1007/s005860100307

    Article  PubMed  CAS  Google Scholar 

  45. AG Huvos (1991) Solitary osteocartilaginous exostosis (osteochondroma) AG Huvos (Eds) Bone Tumors: Diagnosis, Treatment and Prognosis EditionNumber2nd edn W.B. Saunders Philadelphia 253–264

    Google Scholar 

  46. T Nakase A Myoui K Shimada K Kuriyama S Joyama T Miyaji T Tomita H Yoshikawa (2001) ArticleTitleInvolvement of BMP-2 signaling in a cartilage cap in osteochondroma J Orthop Res 19 1085–1088 Occurrence Handle11781009 Occurrence Handle1:CAS:528:DC%2BD38XlslKjsw%3D%3D Occurrence Handle10.1016/S0736-0266(01)00041-9

    Article  PubMed  CAS  Google Scholar 

  47. H Yoshikawa T Nakase A Myoui T Ueda (2004) ArticleTitleBone morphogenetic proteins in bone tumors J Orthop Sci 9 334–340 Occurrence Handle15168194 Occurrence Handle1:CAS:528:DC%2BD2cXksVent78%3D Occurrence Handle10.1007/s00776-004-0764-9

    Article  PubMed  CAS  Google Scholar 

  48. S Okuda A Myoui T Nakase E Wada K Yonenobu H Yoshikawa (2001) ArticleTitleOssification of the ligamentum flavum associated with osteoblastoma: a report of three cases Skelet Radiol 30 402–406 Occurrence Handle1:STN:280:DC%2BD3MvltlKiuw%3D%3D Occurrence Handle10.1007/s002560100324

    Article  CAS  Google Scholar 

  49. T Nakase T Miyaji T Tomita M Kaneko K Kuriyama A Myoui K Sugamoto T Ochi H Yoshikawa (2003) ArticleTitleLocalization of bone morphogenetic protein-2 in human osteoarthritic cartilage and osteophyte Osteoarthritis Cartilage 11 278–284 Occurrence Handle12681954 Occurrence Handle1:STN:280:DC%2BD3s7msFWmsQ%3D%3D Occurrence Handle10.1016/S1063-4584(03)00004-9

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Hoshigaokakoseinenkin Hospital, 4-8-1 Hoshioka, Hirakata, Osaka, 573-8511, Japan

    Takanobu Nakase

  2. Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Japan

    Hideki Yoshikawa

Authors
  1. Takanobu Nakase
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  2. Hideki Yoshikawa
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Corresponding author

Correspondence to Takanobu Nakase.

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T. Nakase is a recipient of the JSBMR Academic Award 2005.

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Nakase, T., Yoshikawa, H. Potential roles of bone morphogenetic proteins (BMPs) in skeletal repair and regeneration. J Bone Miner Metab 24, 425–433 (2006). https://doi.org/10.1007/s00774-006-0718-8

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  • DOI: https://doi.org/10.1007/s00774-006-0718-8

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