Skip to main content
SpringerLink
Log in

The Time-Dependent Manner of Sinusoidal Electromagnetic Fields on Rat Bone Marrow Mesenchymal Stem Cells Proliferation, Differentiation, and Mineralization

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Electromagnetic fields (EMFs) are used clinically to promote fracture healing and slow down osteoporosis without knowledge of optimal parameters and underlying principles. In the present study, we investigate the effects of irritation for different durations with 15 Hz 1 mT sinusoidal EMFs (SEMFs) on rat bone marrow mesenchymal stem cells (BMSCs) proliferation, differentiation, and mineralization potentials. Our results show that SEMFs irritation promote rat BMSCs proliferation in a time-dependent manner, and the expression of osteogenic gen [Cbfa 1/RUNX2, bone sialoprotein (BSP), osteopontin (OPN)], alkaline phosphatase activity, and calcium deposition were enhanced after SEMFs treatment depending on the time duration of treatment. To determine the role of MEK/ERK signaling pathway, U0126, a MEK/ERK inhibitor was used. It can suppress rat BMSCs’ proliferation with or without SEMF exposure, and partly attenuate the expression of osteogenesis related proteins (RUNX2, BSP, OPN) which were improved by SEMF. This finding suggests that the effects of SEMF on rat BMSCs’ proliferation differentiation and mineralization are time duration dependent and MEK/ERK signaling pathway plays important role.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Liu, H. F., Yang, L., He, H. C., Zhou, J., Liu, Y., Wang, C. Y., et al. (2013). Pulsed electromagnetic fields on postmenopausal osteoporosis in southwest China: A randomized, active-controlled clinical trial. Bioelectromagnetics, 34(4), 323–332. doi:10.1002/bem.21770.

    Article  CAS  PubMed  Google Scholar 

  2. Boyette, M. Y., & Herrera-Soto, J. A. (2012). Treatment of delayed and nonunited fractures and osteotomies with pulsed electromagnetic field in children and adolescents. Orthopedics, 35, e1051–e1055.

    Article  PubMed  Google Scholar 

  3. Assiotis, A., Sachinis, N. P., & Chalidis, B. E. (2012). Pulsed electromagnetic fields for the treatment of tibial delayed unions and nonunions. A prospective clinical study and review of the literature. Journal of Orthopaedic Surgery and Research, 7, 24.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Shi, H. F., Xiong, J., Chen, Y. X., Wang, J. F., Qiu, X. S., Wang, Y. H., et al. (2013). Early application of pulsed electromagnetic field in the treatment of postoperative delayed union of long-bone fractures: A prospective randomized controlled study. BMC Musculoskeletal Disorder, 14, 35.

    Article  Google Scholar 

  5. Zhou, J., He, H., Yang, L., Chen, S., Guo, H., Xia, L., et al. (2012). Effects of pulsed electromagnetic fields on bone mass and Wnt/β-catenin signaling pathway in ovariectomized rats. Archives of Medical Research, 43(4), 274–282. doi:10.1016/j.arcmed.2012.06.002.

    Article  CAS  PubMed  Google Scholar 

  6. Skerry, T. M., Pead, M. J., & Lanyon, L. E. (1991). Modulation of bone loss during disuse by pulsed electromagnetic fields. Journal of Orthopaedic Research, 9, 600–608.

    Article  CAS  PubMed  Google Scholar 

  7. Chao, E. Y., Inoue, N., Koo, T. K., & Kim, Y. H. (2004). Biomechanical considerations of fracture treatment and bone quality maintenance in elderly patients and patients with osteoporosis. Clinical Orthopaedics and Related Research, 425, 12–25.

    Article  PubMed  Google Scholar 

  8. Funk, R. H., Monsees, T., & Ozkucur, N. (2009). Electromagnetic effects—From cell biology to medicine. Progress in Histochemistry and Cytochemistry, 43, 177–264.

    Article  PubMed  Google Scholar 

  9. Zhong, C., Zhang, X., Xu, Z., & He, R. (2012). Effects of low-intensity electromagnetic fields on the proliferation and differentiation of cultured mouse bone marrow stromal cells. Physical Therapy, 92, 1208–1219.

    Article  PubMed  Google Scholar 

  10. Sun, L. Y., Hsieh, D. K., Lin, P. C., Chiu, H. T., & Chiou, T. W. (2010). Pulsed electromagnetic fields accelerate proliferation and osteogenic gene expression in human bone marrow mesenchymal stem cells during osteogenic differentiation. Bioelectromagnetics, 31, 209–219.

    Article  CAS  PubMed  Google Scholar 

  11. Jansen, J. H., van der Jagt, O. P., Punt, B. J., Verhaar, J. A., van Leeuwen, J. P., Weinans, H., et al. (2010). Stimulation of osteogenic differentiation in human osteoprogenitor cells by pulsed electromagnetic fields: An in vitro study. BMC Musculoskeletal Disorder, 11, 188.

    Article  Google Scholar 

  12. Zhou, J., Ming, L. G., Ge, B. F., Wang, J. Q., Zhu, R. Q., Wei, Z., et al. (2011). Effects of 50 Hz sinusoidal electromagnetic fields of different intensities on proliferation, differentiation and mineralization potentials of rat osteoblasts. Bone, 49, 753–761.

    Article  CAS  PubMed  Google Scholar 

  13. Yan, J., Dong, L., Zhang, B., & Qi, N. (2010). Effects of extremely low-frequency magnetic field on growth and differentiation of human mesenchymal stem cells. Electromagnetic Biology and Medicine, 29, 165–176.

    Article  CAS  PubMed  Google Scholar 

  14. Zhang, X., Zhang, J., Qu, X., & Wen, J. (2007). Effects of different extremely low-frequency electromagnetic fields on osteoblasts. Electromagnetic Biology and Medicine, 26, 167–177.

    Article  PubMed  Google Scholar 

  15. Ivancsits, S., Pilger, A., Diem, E., Jahn, O., & Rudiger, H. W. (2005). Cell type-specific genotoxic effects of intermittent extremely low-frequency electromagnetic fields. Mutation Research, 583, 184–188.

    Article  CAS  PubMed  Google Scholar 

  16. Jaiswal, R. K., Jaiswal, N., Bruder, S. P., Mbalaviele, G., Marshak, D. R., & Pittenger, M. F. (2000). Adult human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by mitogen-activated protein kinase. Journal of Biological Chemistry, 275, 9645–9652.

    Article  CAS  PubMed  Google Scholar 

  17. Ge, C., Xiao, G., Jiang, D., & Franceschi, R. T. (2007). Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development. Journal of Cell Biology, 176, 709–718.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Sreejit, P., Dilip, K. B., & Verma, R. S. (2012). Generation of mesenchymal stem cell lines from murine bone marrow. Cell and Tissue Research, 350, 55–68.

    Article  CAS  PubMed  Google Scholar 

  19. Tondreau, T., Lagneaux, L., Dejeneffe, M., Delforge, A., Massy, M., Mortier, C., et al. (2004). Isolation of BM mesenchymal stem cells by plastic adhesion or negative selection: Phenotype, proliferation kinetics and differentiation potential. Cytotherapy, 6, 372–379.

    Article  CAS  PubMed  Google Scholar 

  20. Beyer, N. N., & Da, S. M. L. (2006). Mesenchymal stem cells: Isolation, in vitro expansion and characterization. The Handbook of Experimental Pharmacology, 174, 249–282.

    Article  Google Scholar 

  21. Robinson, M. J., & Cobb, M. H. (1997). Mitogen-activated protein kinase pathways. Current Opinion in Cell Biology, 9, 180–186.

    Article  CAS  PubMed  Google Scholar 

  22. Griffin, X. L., Costa, M. L., Parsons, N., & Smith, N. (2011). Electromagnetic field stimulation for treating delayed union or non-union of long bone fractures in adults. Cochrane Database of Systematic Reviews, 4, CD008471. doi:10.1002/14651858.CD008471.pub2.

    PubMed  Google Scholar 

  23. Gnecchi, M., & Melo, L. G. (2009). Bone marrow-derived mesenchymal stem cells: Isolation, expansion, characterization, viral transduction, and production of conditioned medium. Methods in Molecular Biology, 482, 281–294.

    Article  CAS  PubMed  Google Scholar 

  24. Comite, P., Cobianchi, L., Avanzini, M. A., Zonta, S., Mantelli, M., Achille, V., et al. (2010). Isolation and ex vivo expansion of bone marrow-derived porcine mesenchymal stromal cells: Potential for application in an experimental model of solid organ transplantation in large animals. Transplantation Proceedings, 42, 1341–1343.

    Article  CAS  PubMed  Google Scholar 

  25. Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., et al. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8, 315–317.

    Article  CAS  PubMed  Google Scholar 

  26. Sun, L. Y., Hsieh, D. K., Yu, T. C., Chiu, H. T., Lu, S. F., Luo, G. H., et al. (2009). Effect of pulsed electromagnetic field on the proliferation and differentiation potential of human bone marrow mesenchymal stem cells. Bioelectromagnetics, 30, 251–260.

    Article  CAS  PubMed  Google Scholar 

  27. Diniz, P., Soejima, K., & Ito, G. (2002). Nitric oxide mediates the effects of pulsed electromagnetic field stimulation on the osteoblast proliferation and differentiation. Nitric Oxide, 7, 18–23.

    Article  CAS  PubMed  Google Scholar 

  28. Esposito, M., Lucariello, A., Riccio, I., Riccio, V., Esposito, V., & Riccardi, G. (2012). Differentiation of human osteoprogenitor cells increases after treatment with pulsed electromagnetic fields. In Vivo, 26, 299–304.

    PubMed  Google Scholar 

  29. Zhong, C., Zhang, X., Xu, Z., & He, R. (2012). Effects of low-intensity electromagnetic fields on the proliferation and differentiation of cultured mouse bone marrow stromal cells. Physical Therapy, 92(9), 1208–1219. doi:10.2522/ptj.20110224.

    Article  PubMed  Google Scholar 

  30. de Girolamo, L., Stanco, D., Galliera, E., Vigano, M., Colombini, A., Setti, S., et al. (2013). Low frequency pulsed electromagnetic field affects proliferation, tissue-specific gene expression, and cytokines release of human tendon cells. Cell Biochemistry and Biophysics, 66(3), 697–708. doi:10.1007/s12013-013-9514-y.

    Article  PubMed  Google Scholar 

  31. 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 

  32. Harada, H., Tagashira, S., Fujiwara, M., Ogawa, S., Katsumata, T., Yamaguchi, A., et al. (1999). Cbfa1 isoforms exert functional differences in osteoblast differentiation. Journal of Biological Chemistry, 274, 6972–6978.

    Article  CAS  PubMed  Google Scholar 

  33. Jimenez, M. J., Balbin, M., Lopez, J. M., Alvarez, J., Komori, T., & Lopez-Otin, C. (1999). Collagenase 3 is a target of Cbfa1, a transcription factor of the runt gene family involved in bone formation. Molecular and Cellular Biology, 19, 4431–4442.

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Ziros, P. G., Gil, A. P., Georgakopoulos, T., Habeos, I., Kletsas, D., Basdra, E. K., et al. (2002). The bone-specific transcriptional regulator Cbfa1 is a target of mechanical signals in osteoblastic cells. Journal of Biological Chemistry, 277, 23934–23941.

    Article  CAS  PubMed  Google Scholar 

  35. Orimo, H., & Shimada, T. (2008). The role of tissue-nonspecific alkaline phosphatase in the phosphate-induced activation of alkaline phosphatase and mineralization in SaOS-2 human osteoblast-like cells. Molecular and Cellular Biochemistry, 315, 51–60.

    Article  CAS  PubMed  Google Scholar 

  36. Balcerzak, M., Hamade, E., Zhang, L., Pikula, S., Azzar, G., Radisson, J., et al. (2003). The roles of annexins and alkaline phosphatase in mineralization process. Acta Biochimica Polonica, 50, 1019–1038.

    CAS  PubMed  Google Scholar 

  37. Schonwasser, D. C., Marais, R. M., Marshall, C. J., & Parker, P. J. (1998). Activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway by conventional, novel, and atypical protein kinase C isotypes. Molecular and Cellular Biology, 18, 790–798.

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Nie, K., & Henderson, A. (2003). MAP kinase activation in cells exposed to a 60 Hz electromagnetic field. Journal of Cellular Biochemistry, 90, 1197–1206.

    Article  CAS  PubMed  Google Scholar 

  39. Kovacic, P., & Somanathan, R. (2010). Electromagnetic fields: Mechanism, cell signaling, other bioprocesses, toxicity, radicals, antioxidants and beneficial effects. Journal of Receptors and Signal Transduction Research, 30, 214–226.

    Article  CAS  Google Scholar 

  40. Ke, X. Q., Sun, W. J., Lu, D. Q., Fu, Y. T., & Chiang, H. (2008). 50-Hz magnetic field induces EGF-receptor clustering and activates RAS. International Journal of Radiation Biology, 84, 413–420.

    Article  CAS  PubMed  Google Scholar 

  41. Xiao, G., Jiang, D., Thomas, P., Benson, M. D., Guan, K., Karsenty, G., et al. (2000). MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor, Cbfa1. Journal of Biological Chemistry, 275, 4453–4459.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The study was supported by National Natural Science Foundation of China (Grant No. 51077065).

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, Hubei, China

    Ming-Yu Song, Ji-Zhe Yu, Dong-Ming Zhao, Sheng Wei, Yang Liu, Yue-Ming Hu, Yong Yang & Hua Wu

  2. Navy University of Engineering, Wuhan, 430000, Hubei, China

    Wen-Chun Zhao

Authors
  1. Ming-Yu Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ji-Zhe Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dong-Ming Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sheng Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yue-Ming Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wen-Chun Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hua Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yong Yang or Hua Wu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Song, MY., Yu, JZ., Zhao, DM. et al. The Time-Dependent Manner of Sinusoidal Electromagnetic Fields on Rat Bone Marrow Mesenchymal Stem Cells Proliferation, Differentiation, and Mineralization. Cell Biochem Biophys 69, 47–54 (2014). https://doi.org/10.1007/s12013-013-9764-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-013-9764-8

Keywords

Search

Navigation