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Osteoblasts Subjected to Mechanical Strain Inhibit Osteoclastic Differentiation and Bone Resorption in a Co-Culture System

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Abstract

Bone remodeling is strictly mediated by the coupled activities of osteoblasts and osteoclasts, which are responsible for bone formation and resorption, respectively. Although many papers have been published on the mechanical responses of osteoblasts and osteoclasts, little is known about their communication during mechanical loading. In this study, a novel co-culture system was first established using Transwell culture inserts; MC3T3-E1 cells were embedded in the lower compartment of the inserts, and RAW264.7 cells were co-cultured in the upper compartment. The MC3T3-E1 cells were subjected to a mechanical strain of 2500 με at 0.5 Hz to investigate the effect of strain-loaded osteoblasts on co-cultured osteoclasts. The results showed that osteoblast-like cells were activated with an increase of alkaline phosphatase (ALP) activities. The strain-conditioned medium caused decreased activity of tartrate-resistant acid phosphatase and reduced the number of mature multinucleated osteoclasts, which subsequently resulted in the suppressed formation of resorption pits. The expression levels of cathepsin-K and matrix metalloproteinase-9 were also depressed by the strain-conditioned medium. In addition, we found that the expression ratio between osteoprotegerin (OPG) and receptor activator of NF-kB ligand in osteoblasts was significantly up-regulated due to the enhanced levels of OPG. In summary, we conclude that the strain-stimulated osteoblasts inhibited the differentiation and bone resorption of osteoclasts and that the mechanism was associated with the increased secretion of OPG in osteoblasts.

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References

  1. Asagiri, M., and H. Takayanagi. The molecular understanding of osteoclast differentiation. Bone 40(2):251–264, 2007.

    Article  PubMed  CAS  Google Scholar 

  2. Brockstedt, H., J. Bollerslev, F. Melsen, et al. Cortical bone remodeling in autosomal dominant osteopetrosis: a study of two different phenotypes. Bone 18(1):67–72, 1996.

    Article  PubMed  CAS  Google Scholar 

  3. Cheng, T., N. J. Pavlos, C. Wang, et al. Mutations within the TNF-like core domain of RANKL impair osteoclasts differentiation and activation. Mol. Endocrinol. 23(1):35–46, 2009.

    Article  PubMed  CAS  Google Scholar 

  4. Dalbeth, N., B. Pool, T. Smith, et al. Circulating mediators of bone remodeling in psoriatic arthritis: implication for disordered osteoclastogenesis and bone erosion. Arthritis Res. Ther. 12(4):R164, 2010.

    Article  PubMed  Google Scholar 

  5. Deyama, Y., S. Takeyama, M. Koshikawa, et al. Osteoblast maturation suppressed osteoclastogenesis in coculture with bone marrow cells. Biochem. Biophys. Res. Commun. 274(1):249–254, 2000.

    Article  PubMed  CAS  Google Scholar 

  6. Di Palma, F., M. Douet, C. Boachon, et al. Physiological strains induce differentiation in human osteoblasts cultured on orthopaedic biomaterial. Biomaterials 24(18):3139–3151, 2003.

    Article  PubMed  Google Scholar 

  7. Eriksen, E. F. Cellular mechanisms of bone remodeling. Rev. Endocr. Metab. Disord. 11(4):219–227, 2010.

    Article  PubMed  Google Scholar 

  8. Guo, C., Y. X. Yan, X. Z. Zhang, et al. Effects of mechanical strain strength on differentiation of mouse monocytes RAW264.7 into osteoclasts. J. Clin. Rehabil. Tissue Eng. Res. 13(37):7211–7216, 2009; in Chinese.

    CAS  Google Scholar 

  9. Hatherell, K., P. O. Couraud, I. A. Romero, et al. Development of a three-dimensional, all-human in vitro model of the blood–brain barrier using mono-, co-, and tri-cultivation Transwell models. J. Neurosci. Methods 199(2):223–229, 2011.

    Article  PubMed  Google Scholar 

  10. Ichimiya, H., T. Takahashi, W. Ariyoshi, et al. Compressive mechanical stress promotes osteoclast formation through RANKL expression on synovial cells. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 103(3):334–341, 2007.

    Article  PubMed  Google Scholar 

  11. Jones, G. L., A. Motta, M. J. Marshall, et al. Osteoblast: osteoclast co-cultures on silk fibroin, chitosan and PLLA films. Biomaterials 30(29):5376–5384, 2009.

    Article  PubMed  CAS  Google Scholar 

  12. Kadow-Romacker, A., J. E. Hoffmann, G. Duda, et al. Effect of mechanical stimulation on osteoblast- and osteoclast-like cells in vitro. Cells Tissues Organs 190(2):61–68, 2009.

    Article  PubMed  CAS  Google Scholar 

  13. Kreja, L., A. Liedert, S. Hasni, et al. Mechanical regulation of osteoclastic genes in human osteoblasts. Biochem. Biophys. Res. Commun. 368(3):582–587, 2008.

    Article  PubMed  CAS  Google Scholar 

  14. Lemaire, V., F. L. Tobin, L. D. Greller, et al. Modeling the interactions between osteoblast and osteoclast activities in bone remodeling. J. Theor. Biol. 229(3):293–309, 2004.

    Article  PubMed  CAS  Google Scholar 

  15. Lerner, U. H. Bone remodeling in post-menopausal osteoporosis. J. Dent. Res. 85(7):584–595, 2006.

    Article  PubMed  CAS  Google Scholar 

  16. Mullender, M., A. J. El Haj, Y. Yang, et al. Mechanotransduction of bone cells in vitro: mechanobiology of bone tissue. Med. Biol. Eng. Comput. 42(1):14–21, 2004.

    Article  PubMed  CAS  Google Scholar 

  17. Nabavi, N., A. Khandani, A. Camirand, et al. Effects of microgravity on osteoclast bone resorption and osteoblast cytoskeletal organization and adhesion. Bone 49(5):965–974, 2011.

    Article  PubMed  Google Scholar 

  18. Quinn, J. M., and M. T. Gillespie. Modulation of osteoclast formation. Biochem. Biophys. Res. Commun. 328(3):739–745, 2005.

    Article  PubMed  CAS  Google Scholar 

  19. Schriefer, J. L., S. J. Warden, L. K. Saxon, et al. Cellular accommodation and the response of bone to mechanical loading. J Biomech. 38(9):1838–1845, 2005.

    Article  PubMed  Google Scholar 

  20. Sundaram, K., R. Nishimura, J. Senn, et al. RANK ligand signaling modulates the matrix metalloproteinase-9 gene expression during osteoclast differentiation. Exp. Cell Res. 313(1):168–178, 2007.

    Article  PubMed  CAS  Google Scholar 

  21. Suzuki, N., Y. Yoshimura, Y. Deyama, et al. Mechanical stress directly suppresses osteoclast differentiation in RAW 264.7 cells. Int. J. Mol. Med. 21(3):291–296, 2008.

    PubMed  CAS  Google Scholar 

  22. Tan, S. D., T. J. de Vries, A. M. Kuijpers-Jagtman, et al. Osteocytes subjected to fluid flow inhibit osteoclast formation and bone resorption. Bone 41(5):745–751, 2007.

    Article  PubMed  CAS  Google Scholar 

  23. Tang, L., Z. Lin, and Y. M. Li. Effects of different magnitudes of mechanical strain on osteoblasts in vitro. Biochem. Biophys. Res. Commun. 344(1):122–128, 2006.

    Article  PubMed  CAS  Google Scholar 

  24. Tang, L. L., Y. L. Wang, J. Pan, et al. The effect of step-wise increased stretching on rat calvarial osteoblast collagen production. J. Biomech. 37(1):157–161, 2004.

    Article  PubMed  Google Scholar 

  25. Troen, B. R. Molecular mechanisms underlying osteoclast formation and activation. Exp. Gerontol. 38(6):605–614, 2003.

    Article  PubMed  CAS  Google Scholar 

  26. Wang, L., J. Y. Li, X. Z. Zhang, et al. Involvement of p38MAPK/NF-κB signaling pathway in osteoblasts differentiation in response to mechanical stretch. Ann. Biomed. Eng. 40(9):1884–1894, 2012.

    Article  PubMed  Google Scholar 

  27. Wang, L., X. Z. Zhang, Y. Guo, et al. Involvement of BMPs/Smad signaling pathway in mechanical response in osteoblasts. Cell. Physiol. Biochem. 26(6):1093–1102, 2010.

    Article  PubMed  Google Scholar 

  28. Xiong, J. H., and C. A. O’Brien. Osteocyte RANKL: new insight into the control of bone remodeling. J. Bone Miner. Res. 27(3):499–505, 2012.

    Article  PubMed  CAS  Google Scholar 

  29. Xiong, J. H., M. Onal, R. L. Jilka, et al. Matrix-embedded cells control osteoclast formation. Nat. Med. 17(10):1235–1241, 2012.

    Article  Google Scholar 

  30. Yan, Y. X., Y. W. Gong, Y. Guo, et al. Mechanical strain regulates osteoblast proliferation through integrin-mediated ERK activation. PLoS One 7(4):e35709, 2012.

    Article  PubMed  CAS  Google Scholar 

  31. Yang, G., M. Zaidi, W. Zhang, et al. Functional grouping of osteoclast genes revealed through microarray analysis. Biochem. Biophys. Res. Commun. 366(2):352–359, 2008.

    Article  PubMed  CAS  Google Scholar 

  32. Zhang, Q. H., X. Liang, B. M. Zhu, et al. Effects of fluid shear stress on mRNA expression of carbonic anhydrase II in polarized rat osteoclasts. Cell Biol. Int. 30(9):714–720, 2006.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from the National Nature Science Foundation of China (No. 10832012), the Tianjin Science Foundation of China (No. 10JCYBJC14700), the Tianjin Science Foundation of China (No. 13JCQNJC13200) and the Tianjin Public Health Bureau Science Foundation of China (No. 2010KY03).

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All authors certify that they have no financial or personal relationships that could inappropriately influence or bias this work.

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Authors and Affiliations

  1. Institute of Medical Equipment of the Academy of Military Medical Sciences, No. 106 Wandong Road, Hedong District, Tianjin, 300161, China

    Jianyu Li, Zongming Wan, Hao Li, Ruixin Li, Yong Guo, Wei Chen, Xinchang Zhang & Xizheng Zhang

  2. Logistics College of People’s Armed Police Forces, Tianjin, 300162, China

    Jianyu Li, Zongming Wan, Lu Liu & Xinchang Zhang

  3. Key Laboratory of Artificial Cell, Tianjin Third Central Hospital, Tianjin, 300170, China

    Hui Liu

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  1. Jianyu Li
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  2. Zongming Wan
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  4. Hao Li
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  5. Lu Liu
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Correspondence to Xizheng Zhang.

Additional information

Associate Editor Cheng Dong oversaw the review of this article.

Jianyu Li and Zongming Wan contributed equally to this work.

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Li, J., Wan, Z., Liu, H. et al. Osteoblasts Subjected to Mechanical Strain Inhibit Osteoclastic Differentiation and Bone Resorption in a Co-Culture System. Ann Biomed Eng 41, 2056–2066 (2013). https://doi.org/10.1007/s10439-013-0810-x

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  • DOI: https://doi.org/10.1007/s10439-013-0810-x

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