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The Role of Circulating Bone Cell Precursors in Fracture Healing

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Abstract

Fracture healing is a complex process that involves several cell types; as a previous report suggested an increase in osteoblast (OB) precursors in peripheral blood during this process, this paper examines the role of circulating bone cell precursors in this process in the light of a prior suggestion that OB precursors are increased. Nine healthy men less than 60 years old with traumatic fractures were enrolled. The parameters circulating OB precursors (osteocalcin+/alkaline phosphatase+/CD15− cells) and osteoclast precursors (CD14+/CD11b+/vitronectin receptor + cells) were measured by flow cytometry; bone formation markers and TGFβ1, by ELISA; and PTH, by RIA in serum on arrival at the emergency department (baseline) and 15 days after fracture. Bone cell precursors behaved differently during healing. TGFβ1 was inversely correlated with OB number, but increased their degree of maturation at baseline. Bone formation markers and TGFβ1 were increased after fracture, whereas PTH was decreased. The TGFβ1 increase was directly correlated with age, whereas age was not correlated with the precursors. In conclusion, we confirm the role of TGFβ1 in fracture healing; and its possible role in the control of pre-OB homeostasis. There was no variation in circulating precursor cells during healing, though the increase in TGFβ1 may suggest increased pre-OB maturation and homing to the injured site.

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References

  1. De Vries TJ, Everts V (2009) Osteoclast formation from peripheral blood of patients with bone-lytic diseases. Clin Rev Bone Mineral Met 7:285–292

    Article  Google Scholar 

  2. D’Amelio P, Grimaldi A, Di Bella S, Tamone C, Brianza SZ, Ravazzoli MG, Bernabei P, Cristofaro MA, Pescarmona GP, Isaia G (2008) Risedronate reduces osteoclast precursors and cytokine production in postmenopausal osteoporotic women. J Bone Miner Res 23:373–379

    Article  PubMed  Google Scholar 

  3. D’Amelio P, Grimaldi A, Cristofaro MA, Ravazzoli M, Molinatti PA, Pescarmona GP, Isaia GC (2009) Alendronate reduces osteoclast precursors in osteoporosis. Osteoporos Int (in press)

  4. Gossl M, Modder UI, Atkinson EJ, Lerman A, Khosla S (2008) Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis. J Am Coll Cardiol 52:1314–1325

    Article  PubMed  Google Scholar 

  5. Eghbali-Fatourechi GZ, Lamsam J, Fraser D, Nagel D, Riggs BL, Khosla S (2005) Circulating osteoblast-lineage cells in humans. N Engl J Med 352:1959–1966

    Article  CAS  PubMed  Google Scholar 

  6. Eghbali-Fatourechi GZ, Modder UI, Charatcharoenwitthaya N, Sanyal A, Undale AH, Clowes JA, Tarara JE, Khosla S (2007) Characterization of circulating osteoblast lineage cells in humans. Bone 40:1370–1377

    Article  CAS  PubMed  Google Scholar 

  7. Pirro M, Leli C, Fabbriciani G, Manfredelli MR, Callarelli L, Bagaglia F, Scarponi AM, Mannarino E (2009) Association between circulating osteoprogenitor cell numbers and bone mineral density in postmenopausal osteoporosis. Osteoporos Int (in press)

  8. Tsiridis E, Upadhyay N, Giannoudis P (2007) Molecular aspects of fracture healing: which are the important molecules? Injury 38(Suppl 1):S11–S25

    Article  PubMed  Google Scholar 

  9. Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18:4–25

    Article  CAS  PubMed  Google Scholar 

  10. Devine MJ, Mierisch CM, Jang E, Anderson PC, Balian G (2002) Transplanted bone marrow cells localize to fracture callus in a mouse model. J Orthop Res 20:1232–1239

    Article  PubMed  Google Scholar 

  11. Shirley D, Marsh D, Jordan G, McQuaid S, Li G (2005) Systemic recruitment of osteoblastic cells in fracture healing. J Orthop Res 23:1013–1021

    Article  PubMed  Google Scholar 

  12. Kumagai K, Vasanji A, Drazba JA, Butler RS, Muschler GF (2008) Circulating cells with osteogenic potential are physiologically mobilized into the fracture healing site in the parabiotic mice model. J Orthop Res 26:165–175

    Article  PubMed  Google Scholar 

  13. Lieberman JR, Daluiski A, Einhorn TA (2002) The role of growth factors in the repair of bone. Biology and clinical applications. J Bone Joint Surg Am 84-A:1032–1044

    PubMed  Google Scholar 

  14. Sandberg MM, Aro HT, Vuorio EI (1993) Gene expression during bone repair. Clin Orthop Relat Res 289:292–312

    PubMed  Google Scholar 

  15. Pfeilschifter J, Oechsner M, Naumann A, Gronwald RG, Minne HW, Ziegler R (1990) Stimulation of bone matrix apposition in vitro by local growth factors: a comparison between insulin-like growth factor I, platelet-derived growth factor, and transforming growth factor beta. Endocrinology 127:69–75

    Article  CAS  PubMed  Google Scholar 

  16. Frenz DA, Williams JD, Van de Water TR (1991) Initiation of chondrogenesis in cultured periotic mesenchyme. Synergistic action of transforming growth factor-beta and fibroblast growth factor. Ann NY Acad Sci 630:256–258

    Article  CAS  PubMed  Google Scholar 

  17. Joyce ME, Roberts AB, Sporn MB, Bolander ME (1990) Transforming growth factor-beta and the initiation of chondrogenesis and osteogenesis in the rat femur. J Cell Biol 110:2195–2207

    Article  CAS  PubMed  Google Scholar 

  18. Cipriano CA, Issack PS, Shindle L, Werner CM, Helfet DL, Lane JM (2009) Recent advances toward the clinical application of PTH (1–34) in fracture healing. HSS J 5:149–153

    Article  PubMed  Google Scholar 

  19. D’Amelio P, Grimaldi A, Pescarmona GP, Tamone C, Roato I, Isaia G (2005) Spontaneous osteoclast formation from peripheral blood mononuclear cells in postmenopausal osteoporosis. FASEB J 19:410–412

    PubMed  Google Scholar 

  20. D’Amelio P, Grimaldi A, Di Bella S, Brianza SZ, Cristofaro MA, Tamone C, Giribaldi G, Ulliers D, Pescarmona GP, Isaia G (2008) Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis. Bone 43:92–100

    Article  PubMed  Google Scholar 

  21. Ritchlin CT, Haas-Smith SA, Li P, Hicks DG, Schwarz EM (2003) Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest 111:821–831

    CAS  PubMed  Google Scholar 

  22. Dalbeth N, Smith T, Nicolson B, Clark B, Callon K, Naot D, Haskard DO, McQueen FM, Reid IR, Cornish J (2008) Enhanced osteoclastogenesis in patients with tophaceous gout: urate crystals promote osteoclast development through interactions with stromal cells. Arthritis Rheum 58:1854–1865

    Article  CAS  PubMed  Google Scholar 

  23. Ramnaraine M, Pan W, Clohisy DR (2006) Osteoclasts direct bystander killing of cancer cells in vitro. Bone 38:4–12

    Article  CAS  PubMed  Google Scholar 

  24. Massey HM, Flanagan AM (1999) Human osteoclasts derive from CD14-positive monocytes. Br J Haematol 106:167–170

    Article  CAS  PubMed  Google Scholar 

  25. Shalhoub V, Elliott G, Chiu L, Manoukian R, Kelley M, Hawkins N, Davy E, Shimamoto G, Beck J, Kaufman SA, Van G, Scully S, Qi M, Grisanti M, Dunstan C, Boyle WJ, Lacey DL (2000) Characterization of osteoclast precursors in human blood. Br J Haematol 111:501–512

    Article  CAS  PubMed  Google Scholar 

  26. Faust J, Lacey DL, Hunt P, Burgess TL, Scully S, Van G, Eli A, Qian Y, Shalhoub V (1999) Osteoclast markers accumulate on cells developing from human peripheral blood mononuclear precursors. J Cell Biochem 72:67–80

    Article  CAS  PubMed  Google Scholar 

  27. Matayoshi A, Brown C, DiPersio JF, Haug J, Abu-Amer Y, Liapis H, Kuestner R, Pacifici R (1996) Human blood-mobilized hematopoietic precursors differentiate into osteoclasts in the absence of stromal cells. Proc Natl Acad Sci USA 93:10785–10790

    Article  CAS  PubMed  Google Scholar 

  28. Roato I, Grano M, Brunetti G, Colucci S, Mussa A, Bertetto O, Ferracini R (2005) Mechanisms of spontaneous osteoclastogenesis in cancer with bone involvement. FASEB J 19:228–230

    CAS  PubMed  Google Scholar 

  29. Meyer MH, Meyer RA Jr (2007) Genes with greater up-regulation in the fracture callus of older rats with delayed healing. J Orthop Res 25:488–494

    Article  CAS  PubMed  Google Scholar 

  30. Meyer RA Jr, Meyer MH, Tenholder M, Wondracek S, Wasserman R, Garges P (2003) Gene expression in older rats with delayed union of femoral fractures. J Bone Joint Surg Am 85-A:1243–1254

    PubMed  Google Scholar 

  31. Bostrom MP (1998) Expression of bone morphogenetic proteins in fracture healing. Clin Orthop Relat Res 355:S116–S123

    Article  PubMed  Google Scholar 

  32. Connor JM, Evans DA (1982) Fibrodysplasia ossificans progressiva. The clinical features and natural history of 34 patients. J Bone Joint Surg Br 64:76–83

    CAS  PubMed  Google Scholar 

  33. Bernstein A, Mayr HO, Hube R (2010) Can bone healing in distraction osteogenesis be accelerated by local application of IGF-1 and TGF-beta1? J Biomed Mater Res B Appl Biomater 92:215–225

    PubMed  Google Scholar 

  34. Meyer RA Jr, Tsahakis PJ, Martin DF, Banks DM, Harrow ME, Kiebzak GM (2001) Age and ovariectomy impair both the normalization of mechanical properties and the accretion of mineral by the fracture callus in rats. J Orthop Res 19:428–435

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the Fondazione Internazionale Ricerche Medicina Sperimentale (FIRMS) Compagnia San Paolo. P. D’Amelio was supported by a fellowship from the Regione Piemonte.

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Correspondence to Patrizia D’Amelio.

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The authors have stated that they have no conflict of interest.

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D’Amelio, P., Cristofaro, M.A., Grimaldi, A. et al. The Role of Circulating Bone Cell Precursors in Fracture Healing. Calcif Tissue Int 86, 463–469 (2010). https://doi.org/10.1007/s00223-010-9362-3

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  • DOI: https://doi.org/10.1007/s00223-010-9362-3

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