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Clinical Considerations of Regenerative Medicine in Osteoporosis

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Abstract

Osteoporosis-related fractures may severely limit activities of daily living and may require bed rest, which may become life threatening in elderly people. Osteoporosis has attracted much attention recently because of its severe effects on the daily activities of older people and because it is now treatable, thanks to recent advances in drug discovery. However, these medications have yet to reduce fully the number of fracture cases. On the other hand, declines in the number and function of osteoblasts and mesenchymal stem cells (MSCs) in the bone marrow and within the periosteum lead to reduced osteogenesis and bone formation. Thus, bone regeneration, through induction of MSCs, provides a rational therapeutic strategy for preventing or treating age-related osteoporosis. In this review, I summarize cell-related issues in osteoporosis, stem cell candidates for cell-based therapy, and possible therapeutic strategies for osteoporosis.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Weitzmann MN. The role of inflammatory cytokines, the RANKL/OPG axis, and the immunoskeletal interface in physiological bone turnover and osteoporosis. Scientifica (Cairo). 2013;2013:125705. This paper reviews thoroughly osteoporosis and RANKL/OPG axis.

    Google Scholar 

  2. Todd CJ, Freeman CJ, Camilleri-Ferrante C, et al. Differences in mortality after fracture of hip: the East Anglian audit. BMJ. 1995;310(6984):904–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Prevention and management of osteoporosis. World Health Organization Technical Report Series, 2003; 921:1–164.

  4. David C, Confavreux CB, Mehsen N, Paccou J, Leboime A, Legrand E. Severity of osteoporosis: what is the impact of co-morbidities? Jt Bone Spine. 2010;77 Suppl 2:S103–6.

    Article  Google Scholar 

  5. Katsara O, Mahaira LG, Iliopoulou EG, et al. Effects of donor age, gender, and in vitro cellular aging on the phenotypic, functional, and molecular characteristics of mouse bone marrow-derived mesenchymal stem cells. Stem Cells Dev. 2011;20(9):1549–61.

    Article  CAS  PubMed  Google Scholar 

  6. Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000;21(2):115–37.

    CAS  PubMed  Google Scholar 

  7. Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest. 2005;115(12):3318–25.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res. 2007;22(3):465–75.

    Article  PubMed  Google Scholar 

  9. Giampietro PF, McCarty C, Mukesh B, et al. The role of cigarette smoking and statins in the development of postmenopausal osteoporosis: a pilot study utilizing the Marshfield Clinic Personalized Medicine Cohort. Osteoporos Int. 2010;21(3):467–77.

    Article  CAS  PubMed  Google Scholar 

  10. Urano T, Shiraki M, Ezura Y, et al. Association of a single-nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 gene with bone mineral density. J Bone Miner Metab. 2004;22(4):341–5.

    CAS  PubMed  Google Scholar 

  11. Turgeman G, Zilberman Y, Zhou S, et al. Systemically administered rhBMP-2 promotes MSC activity and reverses bone and cartilage loss in osteopenic mice. J Cell Biochem. 2002;86(3):461–74.

    Article  CAS  PubMed  Google Scholar 

  12. Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292(5819):154–6.

    Article  CAS  PubMed  Google Scholar 

  13. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145–7.

    Article  CAS  PubMed  Google Scholar 

  14. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.

    Article  CAS  PubMed  Google Scholar 

  15. Yu J, Vodyanik MA, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858):1917–20.

    Article  CAS  PubMed  Google Scholar 

  16. Mikami Y, Matsumoto T, Kano K, Toriumi T, Somei M, Honda MJ, et al. Current status of drug therapies for osteoporosis and the search for stem cells adapted for bone regenerative medicine. Anat Sci Int. 2014;89(1):1–10. This is one of the few reviews to describe potential therapies for osteoporosis using stem cells.

    Article  CAS  PubMed  Google Scholar 

  17. Ito H. Chemokines in mesenchymal stem cell therapy for bone repair: a novel concept of recruiting mesenchymal stem cells and the possible cell sources. Mod Rheumatol. 2011;21(2):113–21.

    Article  CAS  PubMed  Google Scholar 

  18. Tavassoli M, Crosby WH. Transplantation of marrow to extramedullary sites. Science. 1968;161(3836):54–6. This paper reviews the current knowledge of the migration of mesenchymal stem cells.

    Article  CAS  PubMed  Google Scholar 

  19. Jones E, McGonagle D. Human bone marrow mesenchymal stem cells in vivo. Rheumatology (Oxford). 2008;47(2):126–31.

    CAS  Google Scholar 

  20. Gruber R, Mayer C, Bobacz K, Krauth MT, Graninger W, Luyten FP, et al. Effects of cartilage-derived morphogenetic proteins and osteogenic protein-1 on osteochondrogenic differentiation of periosteum-derived cells. Endocrinology. 2001;142(5):2087–94.

    CAS  PubMed  Google Scholar 

  21. Farrington-Rock C, Crofts NJ, Doherty MJ, Ashton BA, Griffin-Jones C, Canfield AE. Chondrogenic and adipogenic potential of microvascular pericytes. Circulation. 2004;110(15):2226–32.

    Article  CAS  PubMed  Google Scholar 

  22. Lee JY, Qu-Petersen Z, Cao B, et al. Clonal isolation of muscle-derived cells capable of enhancing muscle regeneration and bone healing. J Cell Biol. 2000;150(5):1085–100.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Kuznetsov SA, Mankani MH, Gronthos S, Satomura K, Bianco P, Robey PG. Circulating skeletal stem cells. J Cell Biol. 2001;153(5):1133–40.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Chen HT, Lee MJ, Chen CH, et al. Proliferation and differentiation potential of human adipose-derived mesenchymal stem cells isolated from elderly patients with osteoporotic fractures. J Cell Mol Med. 2012;16(3):582–93.

    Article  CAS  PubMed  Google Scholar 

  25. Lavoie JF, Biernaskie JA, Chen Y, Bagli D, Alman B, Kaplan DR, et al. Skin-derived precursors differentiate into skeletogenic cell types and contribute to bone repair. Stem Cells Dev. 2009;18(6):893–906.

    Article  CAS  PubMed  Google Scholar 

  26. Bi Y, Ehirchiou D, Kilts TM, et al. Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nat Med. 2007;13(10):1219–27.

    Article  CAS  PubMed  Google Scholar 

  27. Atesok K, Doral MN, Bilge O, Sekiya I. Synovial stem cells in musculoskeletal regeneration. J Am Acad Orthop Surg. 2013;21(4):258–9.

    Article  PubMed  Google Scholar 

  28. Liu Y, Wu J, Zhu Y, Han J. Therapeutic application of mesenchymal stem cells in bone and joint diseases. Clin Exp Med. 2014;14(1):13–24. This is one of the few reviews to describe potential therapies for osteoporosis using stem cells.

    Article  CAS  PubMed  Google Scholar 

  29. Bruder SP, Fink DJ, Caplan AI. Mesenchymal stem cells in bone development, bone repair, and skeletal regeneration therapy. J Cell Biochem. 1994;56(3):283–94.

    Article  CAS  PubMed  Google Scholar 

  30. Nuttall ME, Patton AJ, Olivera DL, Nadeau DP, Gowen M. Human trabecular bone cells are able to express both osteoblastic and adipocytic phenotype: implications for osteopenic disorders. J Bone Miner Res. 1998;13(3):371–82.

    Article  CAS  PubMed  Google Scholar 

  31. Marie PJ. Targeting integrins to promote bone formation and repair. Nat Rev Endocrinol. 2013;9(5):288–95. This paper describes one of the potential strategies for treatment of osteoporosis using stem cells.

    Article  CAS  PubMed  Google Scholar 

  32. Guan M, Yao W, Liu R, et al. Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass. Nat Med. 2012;18(3):456–62. This presents one of the potential strategies for treatment of osteoporosis using stem cells.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Yao W, Guan M, Jia J, et al. Reversing bone loss by directing mesenchymal stem cells to bone. Stem Cells. 2013;31(9):2003–14. This paper presents one of the potential strategies for treatment of osteoporosis using stem cells.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

The author would like to thank Dr. EM Schwarz of the University of Rochester Medical Center and Dr. RE Guldberg of Georgia Institute of Technology for their review of the manuscript.

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Conflict of Interest

H Ito declares no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. The Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo, Kyoto, 606-8507, Japan

    Hiromu Ito

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Correspondence to Hiromu Ito.

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Ito, H. Clinical Considerations of Regenerative Medicine in Osteoporosis. Curr Osteoporos Rep 12, 230–234 (2014). https://doi.org/10.1007/s11914-014-0201-8

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  • DOI: https://doi.org/10.1007/s11914-014-0201-8

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