Skip to main content
Log in

Effects of Microgravity Modeled by Large Gradient High Magnetic Field on the Osteogenic Initiation of Human Mesenchymal Stem Cells

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

Microgravity (MG) leads to a decrease in osteogenic potential of human bone marrow-derived mesenchymal stem cells (hMSCs). In the present study, we used large gradient high magnetic field (LGHMF) produced by a superconducting magnet to model MG (LGHMF-MG) and analyzed the effects of LGHMF-MG on survival, cytoskeleton and osteogenic potential of hMSCs. Results showed that the LGHMF-MG treatment for 6 h disrupted the cytoskeleton of hMSCs, and the LGHMF-MG treatment for 24 h led to cell death. LGHMF-MG treatments for 6 h in early stages of osteogenic induction (the pre-treatment before osteogenic induction, the beginning-treatment in the beginning-stage of osteogenic induction and the middle-treatment in the middle-stage of osteogenic induction) resulted in suppression on osteogenesis of hMSCs. The suppression intensity was reduced gradually as the treatment stage of LGHMF-MG was postponed. The LGHMF-MG treatment for 6 h in the ending-stage of osteogenic induction (the ending-treatment) had no obvious effect on osteogenesis of hMSCs. These results indicated that LGHMF-MG should affect the initiation of osteogenesis. Finally, the possible mechanism for the inhibition effect of LGHMF-MG on osteogenesis of hMSCs is discussed.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Lang, T., LeBlanc, A., Evans, H., Lu, Y., Genant, H., & Yu, A. (2004). Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. Journal of Bone and Mineral Research, 19, 1006–1012.

    Article  PubMed  Google Scholar 

  2. Ding, M., Odgaard, A., Linde, F., & Hvid, I. (2002). Age-related variations in the microstructure of human tibial cancellous bone. Journal of Orthopaedic Research, 20, 615–621.

    Article  PubMed  Google Scholar 

  3. Collet, P., Uebelhart, D., Vico, L., et al. (1997). Effects of 1- and 6-month spaceflight on bone mass and biochemistry in two humans. Bone, 20, 547–551.

    Article  CAS  PubMed  Google Scholar 

  4. Carmeliet, G., Nys, G., Stockmans, I., & Bouillon, R. (1998). Gene expression related to the differentiation of osteoblastic cells is altered by microgravity. Bone, 22, 139S–143S.

    Article  CAS  PubMed  Google Scholar 

  5. Landis, W. J., Hodgens, K. J., Block, D., Toma, C. D., & Gerstenfeld, L. C. (2000). Spaceflight effects on cultured embryonic chick bone cells. Journal of Bone and Mineral Research, 15, 1099–1112.

    Article  CAS  PubMed  Google Scholar 

  6. Zayzafoon, M., Gathings, W. E., & McDonald, J. M. (2004). Modeled microgravity inhibits osteogenic differentiation of human mesenchymal stem cells and increases adipogenesis. Endocrinology, 145, 2421–2432.

    Article  CAS  PubMed  Google Scholar 

  7. Saxena, R., Pan, G., & McDonald, J. M. (2007). Osteoblast and osteoclast differentiation in modeled microgravity. Annals of the New York Academy of Sciences, 1116, 494–498.

    Article  CAS  PubMed  Google Scholar 

  8. Tamma, R., Colaianni, G., Camerino, C., et al. (2009). Microgravity during spaceflight directly affects in vitro osteoclastogenesis and bone resorption. The FASEB Journal, 23, 2549–2554.

    Article  CAS  PubMed  Google Scholar 

  9. Rucci, N., Rufo, A., Alamanou, M., & Teti, A. (2007). Modeled microgravity stimulates osteoclastogenesis and bone resorption by increasing osteoblast RANKL/OPG ratio. Journal of Cellular Biochemistry, 100, 464–473.

    Article  CAS  PubMed  Google Scholar 

  10. Saxena, R., Pan, G., Dohm, E. D., & McDonald, J. M. (2010). Modeled microgravity and hindlimb unloading sensitize osteoclast precursors to RANKL-mediated osteoclastogenesis. Journal of Bone and Mineral Metabolism. doi:10.1007/s00774-010-0201-4.

    PubMed  Google Scholar 

  11. Qiang, Z., Guoping, H., Jinfeng, Y., et al. (2007). Could the effect of modeled microgravity on osteogenic differentiation of human mesenchymal stem cells be reversed by regulation of signaling pathways? Biological Chemistry, 388, 755–763.

    Article  Google Scholar 

  12. Pittenger, M. F., Mackay, A. M., Beck, S. C., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284, 143–147.

    Article  CAS  PubMed  Google Scholar 

  13. Franceschi, R. T., & Xiao, G. (2003). Regulation of the osteoblast-specific transcription factor, Runx2: responsiveness to multiple signal transduction pathways. Journal of Cellular Biochemistry, 88, 446–454.

    Article  CAS  PubMed  Google Scholar 

  14. Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L., & Karsenty, G. (1997). Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell, 89, 747–754.

    Article  CAS  PubMed  Google Scholar 

  15. Uva, B. M., Masini, M. A., Sturla, M., et al. (2002). Clinorotation-induced weightlessness influences the cytoskeleton of glial cells in culture. Brain Research, 934, 132–139.

    Article  CAS  PubMed  Google Scholar 

  16. Schatten, H., Lewis, M. L., & Chakrabarti, A. (2001). Spaceflight and clinorotation cause cytoskeleton and mitochondria changes and increases in apoptosis in cultured cells. Acta Astronautica, 49, 399–418.

    Article  CAS  PubMed  Google Scholar 

  17. Wronski, T. J., & Morey-Holton, E. R. (1987). Skeletal response to simulated weightlessness: a comparison of suspension techniques. Aviation Space and Environmental Medicine, 58, 63–68.

    CAS  Google Scholar 

  18. Halloran, B. P., Bikle, D. D., Cone, C. M., & Morey-Holton, E. (1988). Glucocorticoids and inhibition of bone formation induced by skeletal unloading. The American Journal of Physiology, 255, E875–E879.

    CAS  PubMed  Google Scholar 

  19. Dai, Z. Q., Wang, R., Ling, S. K., Wan, Y. M., & Li, Y. H. (2007). Simulated microgravity inhibits the proliferation and osteogenesis of rat bone marrow mesenchymal stem cells. Cell Proliferation, 40, 671–684.

    Article  CAS  PubMed  Google Scholar 

  20. Meyers, V. E., Zayzafoon, M., Gonda, S. R., Gathings, W. E., & McDonald, J. M. (2004). Modeled microgravity disrupts collagen I/integrin signaling during osteoblastic differentiation of human mesenchymal stem cells. Journal of Cellular Biochemistry, 93, 697–707.

    Article  CAS  PubMed  Google Scholar 

  21. Brooks, J. S., Reavis, J. A., Medwood, R. A., Stalcup, T. F., & Meisel, M. W. (2000). New opportunities in science, materials, and biological systems in the low-gravity (magnetic levitation) environment. Journal of Applied Physics, 87, 6194–6199.

    Article  CAS  Google Scholar 

  22. Beaugnon, E., & Tournier, R. (1991). Levitation of organic materials. Nature, 349.

  23. Airong, Q., Dachuan, Y., Pengfei, Y., Bin, J., Wei, Z., & Peng, S. (2009). Development of a ground-based simulated experimental platform for gravitational biology. IEEE Transactions on Applied Superconductivity, 19, 42–46.

    Article  Google Scholar 

  24. Wakayama, N. I., Yin, D. C., Harata, K., Kiyoshi, T., Fujiwara, M., & Tanimoto, Y. (2006). Macromolecular crystallization in microgravity generated by a superconducting magnet. Annals of the New York Academy of Sciences, 1077, 184–193.

    Article  CAS  PubMed  Google Scholar 

  25. Beuls, E., Van Houdt, R., Leys, N., Dijkstra, C., Larkin, O., & Mahillon, J. (2009). Bacillus thuringiensis conjugation in simulated microgravity. Astrobiology, 9, 797–805.

    Article  CAS  PubMed  Google Scholar 

  26. Hammer, B. E., Kidder, L. S., Williams, P. C., & Xu, W. W. (2009). Magnetic levitation of MC3T3 osteoblast cells as a ground-based simulation of microgravity. Microgravity Science and Technology, 21, 311–318.

    Article  CAS  PubMed  Google Scholar 

  27. Airong, Q., Wei, Z., Yuanyuan, W., et al. (2008). Gravitational environment produced by superconducting magnet affects osteoblast morphology and functions. Acta Astronautica, 63, 929–946.

    Article  Google Scholar 

  28. Ying, X., Qiang, Z., Bingbing, J., et al. (2007). Ex vivo expansion, adipogenesis and neurogenesis of cryopreserved human bone marrow mesenchymal stem cells. Cell Biology International, 31, 444–450.

    Article  Google Scholar 

  29. Liyan, Q., & Jinfu, W. (2004). Expansion and chondrogenic induction of human bone mesenchymal stem cells. Journal of Zhejiang University (Science Edition), 31, 337–342.

    Google Scholar 

  30. Meyers, V. E., Zayzafoon, M., Douglas, J. T., & McDonald, J. M. (2005). RhoA and cytoskeletal disruption mediate reduced osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells in modeled microgravity. Journal of Bone and Mineral Research, 20, 1858–1866.

    Article  CAS  PubMed  Google Scholar 

  31. Sundaresan, A., Risin, D., & Pellis, N. R. (2002). Loss of signal transduction and inhibition of lymphocyte locomotion in a ground-based model of microgravity. In Vitro Cellular & Developmental Biology Animal, 38, 118–122.

    Article  Google Scholar 

  32. Crawford-Young, S. J. (2006). Effects of microgravity on cell cytoskeleton and embryogenesis. The International Journal of Developmental Biology, 50, 183–191.

    Article  PubMed  Google Scholar 

  33. Klaus, D. M. (2001). Clinostats and bioreactors. Gravitational and Space Biology Bulletin, 14, 55–64.

    CAS  PubMed  Google Scholar 

  34. Brown, A. H., Chapman, D. K., Heathcote, D. G., & Johnsson, A. (1993). Clinorotation is not always equivalent to weightlessness. ASGSB Bull, 7.

  35. Kaysen, J. H., Campbell, W. C., Majewski, R. R., et al. (1999). Select de novo gene and protein expression during renal epithelial cell culture in rotating wall vessels is shear stress dependent. The Journal of Membrane Biology, 168, 77–89.

    Article  CAS  PubMed  Google Scholar 

  36. Papaseit, C., Pochon, N., & Tabony, J. (2000). Microtubule self-organization is gravity-dependent. Proceedings of the National Academy of Sciences of the United States of America, 97, 8364–8368.

    Article  CAS  PubMed  Google Scholar 

  37. Neurath, P. W. (1968). High gradient magnetic field inhibits embryonic development of frogs. Nature, 219, 1358–1359.

    Article  CAS  PubMed  Google Scholar 

  38. Airong, Q., Shengmeng, D., Xiang, G., et al. (2009). cDNA microarray reveals the alterations of cytoskeleton-related genes in osteoblast under high magneto-gravitational environment. Acta Biochimica et Biophysica Sinica (Shanghai), 41, 561–577.

    Article  Google Scholar 

  39. Airong, Q., Lifang, H., Xiang, G., et al. (2009). Large gradient high magnetic field affects the association of MACF1 with actin and microtubule cytoskeleton. Bioelectromagnetics, 30, 545–555.

    Article  Google Scholar 

  40. Zhou, S., Eid, K., & Glowacki, J. (2004). Cooperation between TGF-beta and Wnt pathways during chondrocyte and adipocyte differentiation of human marrow stromal cells. Journal of Bone and Mineral Research, 19, 463–470.

    Article  CAS  PubMed  Google Scholar 

  41. Lian, J. B., Stein, G. S., Javed, A., et al. (2006). Networks and hubs for the transcriptional control of osteoblastogenesis. Reviews in Endocrine & Metabolic Disorders, 7, 1–16.

    Article  CAS  Google Scholar 

  42. Kostenuik, P. J., Harris, J., Halloran, B. P., Turner, R. T., Morey-Holton, E. R., & Bikle, D. D. (1999). Skeletal unloading causes resistance of osteoprogenitor cells to parathyroid hormone and to insulin-like growth factor-I. Journal of Bone and Mineral Research, 14, 21–31.

    Article  CAS  PubMed  Google Scholar 

  43. Clark, E. A., King, W. G., Brugge, J. S., Symons, M., & Hynes, R. O. (1998). Integrin-mediated signals regulated by members of the rho family of GTPases. The Journal of Cell Biology, 142, 573–586.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Dr. Chris Wood in Zhejiang University and Dr. Hongqi Liu in Thomas Jefferson University for critical reading of the manuscript. This work was supported by Scientific Research from the Scientific Foundation of Zhejiang (2009C13020), National Science Fund of China (30971460).

Disclosures

The authors indicate no potential conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Peng Shang or Jinfu Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shi, D., Meng, R., Deng, W. et al. Effects of Microgravity Modeled by Large Gradient High Magnetic Field on the Osteogenic Initiation of Human Mesenchymal Stem Cells. Stem Cell Rev and Rep 6, 567–578 (2010). https://doi.org/10.1007/s12015-010-9182-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-010-9182-x

Keywords

Navigation