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Regional and cellular localisation of BMPs and their inhibitors’ expression in human fractures

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Abstract

The objective of this study was to determine whether BMP-2 and -14, noggin, and chordin could be detected in human fractures and to assess their regional and cellular distribution. The expression of these proteins was detected by immunohistochemistry in an archive of human fractures. BMP-2 and BMP-14 expression was strongest in areas of cartilage formation and, to a lesser extent, in areas of bone formation. Within areas of cartilage formation, both BMP-2 and BMP-14 were expressed more strongly by the non-hypertrophic chondrocytes. The BMP inhibitors noggin and chordin were also expressed most intensely in areas of cartilage formation and there was no difference in their expression between the non-hypertrophic and hypertrophic chondrocytes. Our study demonstrates the expression of BMP-14 and the BMP inhibitors in human fractures for the first time, and our findings will contribute to an improved understanding of the physiological processes in bone repair.

Résumé

Le but de cette étude est de déterminer si la BMP-2 et la BMP-14 et leurs inhibiteurs noggin et chordin peuvent être détectées dans les fractures chez l’homme, avec une évaluation de leur distribution cellulaire et régionale. Matériels et méthode: l’expression de ces protéines est détectée par immunohistochimie. Résultats: la BMP-2 et la BMP-14 s’expriment de façon importante au niveau de la formation du cartilage et au niveau de la restauration osseuse. Au niveau du cartilage, la BMP-2 et la BMP-14 s’expriment surtout au niveau des chondrocytes non hypertrophiques. Les inhibiteurs de la BMP s’expriment également au niveau de la formation cartilagineuse, il n’y a pas de différence dans leur expression pour les chondrocytes non hyperthrophiques ou hyperthrophiques. En conclusion: notre étude démontre que l’expression de la BMP-14 et de ses inhibiteurs peuvent être détectées dans les fractures chez l’homme. Nos constatations doivent contribuer à une meilleure compréhension du processus de réparation osseuse.

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References

  1. Abe E, Yamamoto M, Taguchi Y, Lecka-Czernik B, O’Brien CA, Economides AN, Stahl N, Jilka RL, Manolagas SC (2000) Essential requirement of BMPs-2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: antagonism by noggin. J Bone Miner Res 15:663–673

    Article  PubMed  CAS  Google Scholar 

  2. Andrew JG, Hoyland JA, Freemont AJ, Marsh DR (1995) Platelet-derived growth factor expression in normally healing human fractures. Bone 16:455–460

    PubMed  CAS  Google Scholar 

  3. Bishop GB, Einhorn TA (2007) Current and future clinical applications of bone morphogenetic proteins in orthopaedic trauma surgery. Int Orthop 31:721–727

    Article  PubMed  Google Scholar 

  4. Borovecki F, Pecina-Slaus N, Vukicevic S (2007) Biological mechanisms of bone and cartilage remodelling-genomic perspective. Int Orthop 31:799–805

    Article  PubMed  CAS  Google Scholar 

  5. Chang K, Weiss D, Suo J, Vega JD, Giddens D, Taylor WR, Jo H (2007) Bone morphogenic protein antagonists are coexpressed with bone morphogenic protein 4 in endothelial cells exposed to unstable flow in vitro in mouse aortas and in human coronary arteries: role of bone morphogenic protein antagonists in inflammation and atherosclerosis. Circulation 116:1258–1266

    Article  PubMed  CAS  Google Scholar 

  6. Cheng H, Jiang W, Phillips FM, Haydon RC, Peng Y, Zhou L, Luu HH, An N, Breyer B, Vanichakarn P, Szatkowski JP, Park JY, He TC (2003) Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg Am 85-A:1544–1552

    PubMed  Google Scholar 

  7. Chhabra A, Zijerdi D, Zhang J, Kline A, Balian G, Hurwitz S (2005) BMP- 14 deficiency inhibits long bone fracture healing: a biochemical, histologic, and radiographic assessment. J Orthop Trauma 19:629–634

    Article  PubMed  Google Scholar 

  8. Einhorn TA, Majeska RJ, Mohaideen A, Kagel EM, Bouxsein ML, Turek TJ, Wozney JM (2003) A single percutaneous injection of recombinant human bone morphogenetic protein-2 accelerates fracture repair. J Bone Joint Surg Am 85-A:1425–1435

    PubMed  Google Scholar 

  9. Hotten GC, Matsumoto T, Kimura M, Bechtold RF, Kron R, Ohara T, Tanaka H, Satoh Y, Okazaki M, Shirai T, Pan H, Kawai S, Pohl JS, Kudo A (1996) Recombinant human growth/differentiation factor 5 stimulates mesenchyme aggregation and chondrogenesis responsible for the skeletal development of limbs. Growth Factors 13:65–74

    Article  PubMed  CAS  Google Scholar 

  10. Ito H, Akiyama H, Shigeno C, Nakamura T (1999) Noggin and bone morphogenetic protein-4 coordinately regulate the progression of chondrogenic differentiation in mouse clonal EC cells, ATDC5. Biochem Biophys Res Commun 260:240–244

    Article  PubMed  CAS  Google Scholar 

  11. Klein M, Vignaud JM, Hennequin V, Toussaint B, Bresler L, Plenat F, Leclere J, Duprez A, Weryha G (2001) Increased expression of the vascular endothelial growth factor is a pejorative prognosis marker in papillary thyroid carcinoma. J Clin Endocrinol Metab 86:656–658

    Article  PubMed  CAS  Google Scholar 

  12. Kloen P, Di Paola M, Borens O, Richmond J, Perino G, Helfet DL, Goumans MJ (2003) BMP signaling components are expressed in human fracture callus. Bone 33:362–371

    Article  PubMed  CAS  Google Scholar 

  13. Kwong FN, Richardson SM, Evans CH (2008) Chordin knockdown enhances the osteogenic differentiation of human mesenchymal stem cells. Arthritis Res Ther 10:R65

    Article  PubMed  Google Scholar 

  14. Kwong FN, Harris MB (2008) Recent developments in the biology of fracture repair. J Am Acad Orthop Surg (in press)

  15. Mackie EJ, Ahmed YA, Tatarczuch L, Chen KS, Mirams M (2008) Endochondral ossification: how cartilage is converted into bone in the developing skeleton. Int J Biochem Cell Biol 40:46–62

    Article  PubMed  CAS  Google Scholar 

  16. McKay WF, Peckham SM, Badura JM (2007) A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE Bone Graft). Int Orthop 31:729–734

    Article  PubMed  Google Scholar 

  17. Merino R, Macias D, Ganan Y, Economides AN, Wang X, Wu Q, Stahl N, Sampath KT, Varona P, Hurle JM (1999) Expression and function of Gdf-5 during digit skeletogenesis in the embryonic chick leg bud. Dev Biol 206:33–45

    Article  PubMed  CAS  Google Scholar 

  18. Nifuji A, Kellermann O, Noda M (2004) Noggin inhibits chondrogenic but not osteogenic differentiation in mesodermal stem cell line C1 and skeletal cells. Endocrinology 145:3434–3442

    Article  PubMed  CAS  Google Scholar 

  19. Pecina M, Vukicevic S (2007) Biological aspects of bone, cartilage and tendon regeneration. Int Orthop 31:719–720

    Article  PubMed  Google Scholar 

  20. Piccolo S, Sasai Y, Lu B, De Robertis EM (1996) Dorsoventral patterning in Xenopus: inhibition of ventral signals by direct binding of chordin to BMP-4. Cell 86:589–598

    Article  PubMed  CAS  Google Scholar 

  21. Tardif G, Hum D, Pelletier JP, Boileau C, Ranger P, Martel-Pelletier J (2004) Differential gene expression and regulation of the bone morphogenetic protein antagonists follistatin and gremlin in normal and osteoarthritic human chondrocytes and synovial fibroblasts. Arthritis Rheum 50:2521–2530

    Article  PubMed  CAS  Google Scholar 

  22. Tsumaki N, Tanaka K, Arikawa-Hirasawa E, Nakase T, Kimura T, Thomas JT, Ochi T, Luyten FP, Yamada Y (1999) Role of CDMP-1 in skeletal morphogenesis: promotion of mesenchymal cell recruitment and chondrocyte differentiation. J Cell Biol 144:161–173

    Article  PubMed  CAS  Google Scholar 

  23. Wan DC, Pomerantz JH, Brunet LJ, Kim JB, Chou YF, Wu BM, Harland R, Blau HM, Longaker MT (2007) Noggin suppression enhances in vitro osteogenesis and accelerates in vivo bone formation. J Biol Chem 282:26450–26459

    Article  PubMed  CAS  Google Scholar 

  24. Westerhuis RJ, van Bezooijen RL, Kloen P (2005) Use of bone morphogenetic proteins in traumatology. Injury 36:1405–1412

    Article  PubMed  CAS  Google Scholar 

  25. Yoshimura Y, Nomura S, Kawasaki S, Tsutsumimoto T, Shimizu T, Takaoka K (2001) Colocalization of noggin and bone morphogenetic protein-4 during fracture healing. J Bone Miner Res 16:876–884

    Article  PubMed  CAS  Google Scholar 

  26. Zhang D, Ferguson CM, O’Keefe RJ, Puzas JE, Rosier RN, Reynolds PR (2002) A role for the BMP antagonist chordin in endochondral ossification. J Bone Miner Res 17:293–300

    Article  PubMed  CAS  Google Scholar 

  27. Zimmerman LB, De Jesus-Escobar JM, Harland RM (1996) The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4. Cell 86:599–606

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

This study was supported by NIH grant AR 050243.

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Correspondence to Francois N. K. Kwong.

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Kwong, F.N.K., Hoyland, J.A., Evans, C.H. et al. Regional and cellular localisation of BMPs and their inhibitors’ expression in human fractures. International Orthopaedics (SICO 33, 281–288 (2009). https://doi.org/10.1007/s00264-008-0691-z

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  • DOI: https://doi.org/10.1007/s00264-008-0691-z

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