The cell and molecular biology of bone fracture repair: role of the transforming growth factor-ß1 in activation reparative osteogenesis (review)

Authors

  • Stanislav Sagalovsky
  • Matthias Schоnert

DOI:

https://doi.org/10.15674/0030-598720143136-143

Keywords:

osteogenesis, bone fracture healing, transforming growth factor β-1, bone morphogenic protein

Abstract

This paper describes the cellular and molecular mechanisms underlying in the basis of bone fractures healing. It is shown that there are two types of fracture healing. In the case of the primary type bone tissue directly form in zone of damage. In the case of instability of the bone fragments and considerable distance between them the process of restoration of the integrity of the bone goes through several stages including inflammation, migration and proliferation of cells, the formation of tissue-specific structures and the restructuring of the regenerate. At the same time at different stages certain factors affecting the proliferation, differentiation of osteogenic cells and synthesis of extracellular matrix release. Growth factors control the various stages of reparative osteogenesis. In recent years the regulatory role of transforming growth factor beta-1 (TGF-β1) and belonging to his family of bone morphogenetic protein (BMP) in the formation and development of bone regeneration was confirmed. According to modern scientific ideas BMP act as primary activators of differentiation of osteogenic progenitor cells, and mesenchymal cells, and are involved in the processes of bone remodeling and fracture healing. Initially it was thought that TGF-β1 stimulates the proliferation of undifferentiated mesenchymal cells and chondrocytes as well as the production of extracellular matrix during chondrogenesis and enchondral osteogenesis. As shown in recent studies optimizing effect of TGF-β1 on the processes of fracture healing is dose-dependent and requires its constant high concentration. In-depth understanding of the mechanisms of development reparative osteogenesis allows to develop a new strategy for optimization of the process of restoring the integrity of bone broken due to injury.

References

  1. A cost analysis of treatment of tibial fracture nonunion by bone grafting or bone morphogenetic protein-7 / Z. Dahabreh, G. M. Calori, N. K. Kanakaris [et al.] // Int. Orthop. — 2009. — Vol. 33, Issue 5. — P. 1407–1414.
  2. The burden of musculoskeletal conditions at the start of the new millenium // WHO Technical Report Series. Report of a WHO Scientific Group. Geneva: WHO. — 2003. — Vol. 919. — Р. 1–218.
  3. Court-Brown C. M. Epidemiology of adult fractures: a review / C. M. Court-Brown, B. Cesar // Injury. — 2006. — Vol. 37, Issue 8. — P. 691–697.
  4. The epidemiology of fractures / C. M. Court-Brown, S. A. Aitken, D. Forward [et al.] // Rockwood and Green’s Fractures in adults / R. W. Bucholz, C. M. Court-Brown, J. D. Heckman. — 7th edition. — Lippancott Williams&Wilkins, Philadelphia, Pa., USA, 2010. — Р. 53–84.
  5. Marsell R. The biology of fracture healing / R. Marsell, T. A. Einhorn // Injury. — 2011. — Vol. 42, Issue 6. — P. 551–555.
  6. Neve A. Osteoblast physiology in normal and pathological conditions / A. Neve, A. Corrado, F. P. Cantatore // Cell Tissue Res. — 2011. — Vol. 343, Issue 2. — P. 289–302.
  7. Elevated transforming growth factor-beta 1 (TGF-ß1) levels in human fracture healing / K. Sarahrudi, A. Thomas, M. Mousavi [et al.] // Injury. — 2011. — Vol. 42, Issue 8. — P. 833–837.
  8. Tsiridis E. Molecular aspects of fracture healing: which are the important molecules? / E. Tsiridis, N. Upadhyay, P. Giannoudis // Injury. — 2007. — Vol. 38, Issue 1. — P. 11–25.
  9. Santibanez J. E. TGF-ß/TGF-ß receptor system and its role in physiological and pathological conditions / J. E. Santibanez, M. Quintanilla, C. Bernabeu // Clin. Sci. — 2011. — Vol. 121, Issue 6. — P. 233–251.
  10. Fracture repair / C. Sfeir, L. Ho, B. A. Doll [et al.] // Bone regeneration and repair: biology and clinical applications / J. R. Liberman, C. E. Friedlaender, eds. — Humana Press Inc., Totowa; N. J., 2005. — Р. 21–44.
  11. Yamagiwa H. Bone fracture and the healing mechanisms. Histological aspect of fracture healing. Primary and secondary healing / H. Yamagiwa, N. Endo // Clin. Calcium. — 2009. — Vol. 19, Issue 5. — P. 627–633.
  12. Systemic inflammation and fracture healing / O. Bastian, J. Pillay, J. Alblas [et al.] // J. Leukoc. Biol. — 2011. — Vol. 89, Issue 5. — P. 669–673.
  13. Claes L. Fracture healing under healthy and inflammatory conditions / L. Claes, S. Recknagel, A. Ignatius // Nat. Rev. Rheumatol. — 2012. — Vol. 8, Issue 3. — P. 133–143.
  14. Beamer B. Vascular endothelial growth factor: an essential component of angiogenesis and fracture healing / B. Beamer, C. Hettrich, J. Lane // HSSJ. — 2010. — Vol. 6, Issue 1. — P. 85–94.
  15. The early fracture hematoma and its potential role in fracture healing / P. Kolar, K. Schmidt-Bleck, H. Schell [et al.] // Tissue Eng. Part B Rev. — 2010. — Vol. 16, Issue 4. — P. 427–434.
  16. Biological implications of growth factors in bone remodeling following fracture, surgical resection and bonegrafting. Part 1: transforming growth factors, bone morphogenetic proteins and related factors / M. Mori, M. Motohashi, T. Nishikawa [et al.] // Asian J. Oral Maxillofacial Surg. — 2010. — Vol. 22, Issue 3. — P. 117–125.
  17. Giannoudis P. V. Fracture healing and bone repair / P. V. Giannoudis, E. Jones, T. A. Einhorn // Injury. — 2011. — Vol. 42, Issue 6. — P. 549–550.
  18. Claes L. E. Biomechanics of fracture fixation and fracture healing / L. E. Claes, K. Ito // Basic orthopedic biomechanics and mechanobiology / V. C. Mow, R. Huiskes, eds. — 3th edition. — Lippincott Williams & Wilkins, Philadelphia, 2005. — Р. 563–584.
  19. Griffin M. Exploring the application of mesenchimal stem cells in bone repair and regeneration / M. Griffin, S. A. Iqbal, A. Bayat // J. Bone Joint Surg. — 2011. — Vol. 93-B, Issue 4. — P. 427–434.
  20. Bone regeneration and stem cells / K. Arvidson, B. M. Abdallah, L. A. Applegate [et al.] // J. Cell. Mol. Med. — 2011. — Vol. 15, Issue 4. — P. 718–746.
  21. Molecular mechanisms controlling bone formation during fracture healing and distraction osteogenesis / Z. S. Al-Aql, A. S. Alagl, D. T. Graves [et al.] // J. Dent. Res. — 2008. — Vol. 87, Issue 2. — P. 107–118.
  22. Fracture healing and bone repair: an update / T. Tosounidis, G. Kontakis, V. Nikolaeu [et al.] // Trauma. — 2009. — Vol. 11, Issue 3. — P. 145–156.
  23. Osteoblasts: cellular and molecular regulatory mechanisms in fracture healing / A. Hofmann, S. G. Mattyasovsky, C. Brüning [et al.] // Der Orthopäd. — 2009. — Vol. 38, Issue 11. — P. 1009–1019.
  24. Bone remodeling during fracture repair: the cellular picture / A. Schindeler, M. M. McDonald, P. Bokko [et al.] // Semin. Cell Develop. Biol. — 2008. — Vol. 19, Issue 5. — P. 459–466.
  25. Phillips A. M. Overview of the fracture healing cascade / A. M. Phillips // Injury. — 2005. — Vol. 36, Issue 1. — S. 5–7.
  26. Kwong F. N. Recent developments in the biology of fracture repair / F. N. Kwong, M. B. Harris // J. Am. Acad. Orthop. Surg. — 2008. — Vol. 16, Issue 11. — P. 619–625.
  27. Makholm A. M. The role of growth factors on acceleration of bone regeneration during distraction osteogenesis / A. M. Makholm, R. C. Hamdy // Tissue Engineering Part B. — 2013. — Vol. 19, Issue 5. — P. 442–453.
  28. Chen G. TGF-ß and BMP signaling in osteoblast differentiation and bone formation / G. Chen, C. Deng, Y.-P. Li // Int. J. Biol. Sci. — 2012. — Vol. 8, Issue 2. — P. 272–288.
  29. Huang F. Regulation of TGF-ß receptor activity / F. Huang, Y.-G. Chen // Cell Biosci. — 2012. — Vol. 2, Issue 9. — P. 1–9.
  30. Boyce B. F. Biology of RANK, RANKL and Osteoprotegerin / B. F. Boyce, L. Xing // Arthritis Res. Ther. — 2007. — Vol. 9, Issue 1. — S. 1.
  31. Sagalovsky S. Bone remoleling: cellular-molecular biology and role cytokine RANK-RANKL-Osteoprotegerin (OPG) system and growth factors / S. Sagalovsky // Crimea J. Exptl. Clin. Med. — 2013. — Vol. 3, Issue 1–2. — P. 36–44.
  32. Wada T. RANKL-RANK signaling in osteoclastogenesis and bone disease / T. Wada, T. Nakashima, N. Hiroshi, J. M. Penninger // Trends Mol. Med. — 2006. — Vol. 12, Issue 1. — P. 17–25.
  33. Karst M. Roles of stromal cell RANKL, OPG and M-CSF expression in biphasic TGF-beta regulation of osteoblast differentiation / M. Karst, G. Gorny, R. J. Galvin, M. J. Oursler // J. Cell. Physiol. — 2004. — Vol. 200, Issue 1. — P. 99–106.
  34. Nishimura R. A noval role for TGF-ß1 in bone remodeling / R. Nishimura // IBMS Bone Key. — 2009. — Vol. 6. — P. 434–438.
  35. Simpson A. H. R. W. The role of growth factors and related agents in accelerating fracture healing / A. H. R. W. Simpson, L. Mills, B. Noble // J. Bone Joint Surg. — 2006. — Vol. 88-B, Issue 6. — P. 701–705.
  36. Gazzerro E. Bone morphogeneric proteins and their antagonists / E. Gazzerro, E. Canalis // Rev. Endocrinol. Metab. Disord. — 2006. — Vol. 7, Issue 2. — P. 51–65.
  37. Physiological role of bone morphogenetic proteins in osteogenesis / F. Kugimiya, S. Ohba, K. Nakamura [et al.] // J. Bone Miner. Metab. — 2006. — Vol. 24, Issue 1. — P. 95–99.
  38. Marsell R. The role of endogenous bone morphogenetic proteins in normal skeletal repair / R. Marsell, T. A. Einhorn // Bone morphogenetic proteins: applications in orthopaedic and trauma surgery / P. V. Giannoudis, T. A. Einhorn, eds. — United Kingdom: Elsevier, 2010. — P. 9–17.
  39. Dedukh N. V. New technologies in bone regeneration: the use of growth factors / N. V. Dedukh, S. A. Khmyzov, A. A. Tikhonenko // Orthopaedics, Traumatology and Prosthetics. — 2008. — Issue 4. — P. 129–133.
  40. Lissenberg-Thunnissen S. N. Use and efficacy of bone morphogenetic proteins in fracture healing / S. N. Lissenberg-Thunnissen, D. J. J. de Gorter, C. F. M. Sier, I. B. Schipper // Int. Orthop. — 2011. — Vol. 35, Issue 9. — P. 1271–1280.

Downloads

How to Cite

Sagalovsky, S., & Schоnert M. (2014). The cell and molecular biology of bone fracture repair: role of the transforming growth factor-ß1 in activation reparative osteogenesis (review). ORTHOPAEDICS TRAUMATOLOGY and PROSTHETICS, (3), 136–143. https://doi.org/10.15674/0030-598720143136-143

Issue

No. 3 (2014)

Section

DIGESTS AND REVIEWS

License

Copyright (c) 2014 Stanislav Sagalovsky, Matthias Schоnert

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

The authors retain the right of authorship of their manuscript and pass the journal the right of the first publication of this article, which automatically become available from the date of publication under the terms of Creative Commons Attribution License, which allows others to freely distribute the published manuscript with mandatory linking to authors of the original research and the first publication of this one in this journal.

Authors have the right to enter into a separate supplemental agreement on the additional non-exclusive distribution of manuscript in the form in which it was published by the journal (i.e. to put work in electronic storage of an institution or publish as a part of the book) while maintaining the reference to the first publication of the manuscript in this journal.

The editorial policy of the journal allows authors and encourages manuscript accommodation online (i.e. in storage of an institution or on the personal websites) as before submission of the manuscript to the editorial office, and during its editorial processing because it contributes to productive scientific discussion and positively affects the efficiency and dynamics of the published manuscript citation (see The Effect of Open Access).