Skip to main content
Log in

Adipose tissue-derived stem cells in the ovariectomy-induced postmenopausal osteoporosis rat model

  • Original Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

This study investigated the efficacy of adult adipose tissue-derived stem cells in restoring bone using an osteoporotic rat model. Thirty-six female Wistar rats (250–300 g, 12 weeks) were randomized into three equal groups: SHAM group (sham-operated), ovariectomy-induced (OVX) group and OVX with stem cell injection group (OVX with stem). Femur extraction and blood sampling were performed at 5, 6, 7 and 8 weeks. The proximal femoral metaphysis was scanned by micro-CT and evaluated for changes in various histomorphometric parameters. β-catenin expression was determined using H&E and immunohistochemistry. Bone metabolism was assessed using measurements of C-telopeptide of collagen type I (CTX), osteocalcin, and bone alkaline phosphatase (BALP). There was a trend for an increase in the bone mineral density (BMD), bone volume/trabecular bone volume (BV/TV) and trabecular number (Tb.N) in the OVX with stem group as compared with the OVX group, and decrease in the OVX with stem group as compared with SHAM group. The trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) of the OVX group were increased compared with those values in the SHAM and OVX with stem group. BALP levels were higher in the OVX group as compared with that in the other two groups and osteocalcin levels were highest in the SHAM group and slightly increased in the OVX with stem group as compared with the OVX group. This study may help us gain an understanding of the role of MSCs in the pathophysiology and treatment of osteoporosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. E Voskaridou, E Terpos, New insights into the pathophysiology and management of osteoporosis in patients with beta thalassaemia, Br J Haematol, 127, 127 (2004).

    Article  CAS  PubMed  Google Scholar 

  2. RH Christenson, Biochemical markers of bone metabolism: an overview, Clin Biochem, 30, 573 (1997).

    Article  CAS  PubMed  Google Scholar 

  3. JA Kanis, J Kanis, Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report, Osteoporos Int, 4, 368 (1994).

    Article  CAS  PubMed  Google Scholar 

  4. S Khosla, BL Riggs, Pathophysiology of age-related bone loss and osteoporosis, Age, 60, 80 (2005).

    Google Scholar 

  5. AJ Friedenstein, Precursor cells of mechanocytes, Int Rev Cytol, 47, 327 (1976).

    Article  CAS  PubMed  Google Scholar 

  6. SB Park, YJ Lee, CK Chung, Bone mineral density changes after ovariectomy in rats as an osteopenic model: stepwise description of double dorso-lateral approach, J Korean Neurosurg Soc, 48, 309 (2010).

    Article  PubMed Central  PubMed  Google Scholar 

  7. S Khosla, JJ Westendorf, MJ Oursler, Building bone to reverse osteoporosis and repair fractures, J Clin Invest, 118, 421 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. BA Ashton, TD Allen, CR Howlett, et al., Formation of bone and cartilage by marrow stromal cells in diffusion chambers in vivo, Clin Orthop Relat Res, 294 (1980).

    Google Scholar 

  9. AI Caplan, Mesenchymal stem cells, J Orthop Res, 9, 641 (1991).

    Article  CAS  PubMed  Google Scholar 

  10. NA Hanania, KR Chapman, WC Sturtridge, et al., Dose-related decrease in bone density among asthmatic patients treated with inhaled corticosteroids, J Allergy Clin Immunol, 96, 571 (1995).

    Article  CAS  PubMed  Google Scholar 

  11. J Reeve, J Loftus, R Hesp, et al., Biochemical prediction of changes in spinal bone mass in juvenile chronic (or rheumatoid) arthritis treated with glucocorticoids, J Rheumatol, 20, 1189 (1993).

    CAS  PubMed  Google Scholar 

  12. LJ Melton III, EA Chrischilles, C Cooper, et al., Perspective how many women have osteoporosis?, J Bone Miner Res, 7, 1005 (1992).

    Article  PubMed  Google Scholar 

  13. SC Miller, BM Bowman, WS Jee, Available animal models of osteopenia—small and large, Bone, 17, 117S (1995).

    CAS  PubMed  Google Scholar 

  14. F Bauss, DW Dempster, Effects of ibandronate on bone quality: preclinical studies, Bone, 40, 265 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. DN Kalu, The ovariectomized rat model of postmenopausal bone loss, Bone Miner, 15, 175 (1991).

    Article  CAS  PubMed  Google Scholar 

  16. J Gasser, Stem cells in the treatment of osteoporosis, Eur Cell Mater, 6, 21 (2003).

    Google Scholar 

  17. YJ Kim, HK Kim, HH Cho, et al., Direct comparison of human mesenchymal stem cells derived from adipose tissues and bone marrow in mediating neovascularization in response to vascular ischemia, Cell Physiol Biochem, 20, 867 (2007).

    Article  CAS  PubMed  Google Scholar 

  18. SW Cho, HJ Sun, JY Yang, et al., Human adipose tissue-derived stromal cell therapy prevents bone loss in ovariectomized nude mouse, Tissue Eng Part A, 18, 1067 (2012).

    Article  CAS  PubMed  Google Scholar 

  19. EL Fong, CK Chan, SB Goodman, Stem cell homing in musculoskeletal injury, Biomaterials, 32, 395 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. R Pereira, K Halford, M O’hara, et al., Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice, Proc Natl Acad Sci U S A, 92, 4857 (1995).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. J Gao, JE Dennis, RF Muzic, et al., The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion, Cells Tissues Organs, 169, 12 (2001).

    Article  CAS  PubMed  Google Scholar 

  22. K Kumagai, A Vasanji, JA Drazba, et al., Circulating cells with osteogenic potential are physiologically mobilized into the fracture healing site in the parabiotic mice model, J Orthop Res, 26, 165 (2007).

    Article  Google Scholar 

  23. R van Os, A Ausema, B Dontje, et al., Engraftment of syngeneic bone marrow is not more efficient after intrafemoral transplantation than after traditional intravenous administration, Exp Hematol, 38, 1115 (2010).

    Article  PubMed  Google Scholar 

  24. E Seeman, Estrogen, androgen, and the pathogenesis of bone fragility in women and men, Curr Osteoporos Rep, 2, 90 (2004).

    Article  PubMed  Google Scholar 

  25. C Bagi, P Ammann, R Rizzoli, et al., Effect of estrogen deficiency on cancellous and cortical bone structure and strength of the femoral neck in rats, Calcif Tissue Int, 61, 336 (1997).

    Article  CAS  PubMed  Google Scholar 

  26. O Barou, D Valentin, L Vico, et al., High-resolution three-dimensional micro-computed tomography detects bone loss and changes in trabecular architecture early: comparison with DEXA and bone histomorphometry in a rat model of disuse osteoporosis, Invest Radiol, 37, 40 (2002).

    Article  PubMed  Google Scholar 

  27. A Odgaard, Three-dimensional methods for quantification of cancellous bone architecture, Bone, 20, 315 (1997).

    Article  CAS  PubMed  Google Scholar 

  28. J Beck, B Canfield, S Haddock, et al., Three-dimensional imaging of trabecular bone using the computer numerically controlled milling technique, Bone, 21, 281 (1997).

    Article  CAS  PubMed  Google Scholar 

  29. PD Delmas, Biochemical markers of bone turnover, Acta Orthop, 66, 176 (1995).

    Article  Google Scholar 

  30. MS Calvo, DR Eyre, CM Gundberg, Molecular basis and clinical application of biological markers of bone turnover, Endocr Rev, 17, 333 (1996).

    CAS  PubMed  Google Scholar 

  31. P Meunier, C Salson, L Mathieu, et al., Skeletal distribution and biochemical parameters of Paget’s disease, Clin Orthop Relat Res, 37 (1987).

    Google Scholar 

  32. DY Kim, Biochemical markers of bone turnover, Korean J Nucl Med, 33, 341 (1999).

    Google Scholar 

  33. J Scariano, R Glew, C Bou-Serhal, et al., Serum levels of cross-linked N-telopeptides and aminoterminal propeptides of type I collagen indicate low bone mineral density in elderly women, Bone, 23, 471 (1998).

    Article  CAS  PubMed  Google Scholar 

  34. HW Woitge, M Pecherstorfer, Y Li, et al., Novel serum markers of bone resorption: clinical assessment and comparison with established urinary indices, J Bone Miner Res, 14, 792 (1999).

    Article  CAS  PubMed  Google Scholar 

  35. J Zhou, S Chen, H Guo, et al., Electroacupuncture prevents ovariectomy-induced osteoporosis in rats: a randomised controlled trial, Acupunct Med, 30, 37 (2012).

    Article  CAS  PubMed  Google Scholar 

  36. JR Hens, KM Wilson, P Dann, et al., TOPGAL mice show that the canonical Wnt signaling pathway is active during bone development and growth and is activated by mechanical loading in vitro, J Bone Miner Res, 20, 1103 (2005).

    Article  CAS  PubMed  Google Scholar 

  37. GI Im, Intracellular Signal Transduction Pathways and Transcription Factors for Osteogenesis, J Korean Rheum Assoc, 15, 1 (2008).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kyoung Hyo Choi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jeong, J.H., Park, J., Jin, ES. et al. Adipose tissue-derived stem cells in the ovariectomy-induced postmenopausal osteoporosis rat model. Tissue Eng Regen Med 12, 28–36 (2015). https://doi.org/10.1007/s13770-014-0001-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13770-014-0001-3

Key words

Navigation