Skip to main content
SpringerLink
Log in

Flow-Induced Migration of Osteoclasts and Regulations of Calcium Signaling Pathways

  • Published:
Cellular and Molecular Bioengineering Aims and scope Submit manuscript

Abstract

Osteoclasts are large multinucleate cells originating from the fusion of monocytes that are differentiated from hematopoietic stem cells. Although activated osteoclasts preferentially move to the area of microcrack by chemotaxis, whether such mechanical cues as fluid shear stress (FSS) regulate the migration of osteoclasts remains unknown. This study focuses on the effect of FSS on the migration of RAW264.7 monocytes and differentiated osteoclasts, as well as the roles of calcium signaling pathways in cell migration behaviors. We study five calcium signaling pathways, namely, mechanosensitive cation-selective channels (MSCC), phospholipase C, endoplasmic reticulum (ER), adenosine triphosphate, and extracellular calcium. Results show that FSS induces the migration of RAW264.7 cells along flow direction, and the directionality, alignment along the flow direction, and speed of cells are significantly enhanced with the increase in FSS levels. Blocking the pathways of MSCC, ER, or extracellular calcium significantly reduces the migration of RAW264.7 cells along the flow direction. However, the inhibition of calcium signaling pathways does not affect the migration behaviors after inducing RAW264.7 cells for 4 or 8 days with the conditioned medium, Therefore, this study indicates that both undifferentiated monocytes and differentiated osteoclasts tend to migrate along flow direction, furthermore the FSS-induced directional migration of the monocytes is regulated by calcium signaling pathways, but that of differentiated osteoclasts is unaffected.

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Al-Dujaili, S. A., E. Lau, et al. Apoptotic osteocytes regulate osteoclast precursor recruitment and differentiation in vitro. J. Cell Biochem. 112(9):2412–2423, 2011.

    Article  Google Scholar 

  2. Baron, R., L. Neff, et al. Kinetic and cytochemical identification of osteoclast precursors and their differentiation into multinucleated osteoclasts. Am. J. Pathol. 122(2):363–378, 1986.

    Google Scholar 

  3. Baroukh, B., M. Cherruau, et al. Osteoclasts differentiate from resident precursors in an in vivo model of synchronized resorption: a temporal and spatial study in rats. Bone 27(5):627–634, 2000.

    Article  Google Scholar 

  4. Bentolila, V., T. M. Boyce, et al. Intracortical remodeling in adult rat long bones after fatigue loading. Bone 23(3):275–281, 1998.

    Article  Google Scholar 

  5. Boudot, C., Z. Saidak, et al. Implication of the calcium sensing receptor and the phosphoinositide 3-kinase/Akt pathway in the extracellular calcium-mediated migration of RAW 264.7 osteoclast precursor cells. Bone 46(5):1416–1423, 2010.

    Article  Google Scholar 

  6. Bruck, H. A., S. R. McNeill, et al. Digital image correlation using Newton–Raphson method of partial-differential correction. Exp. Mech. 29(3):261–267, 1989.

    Article  Google Scholar 

  7. Brundage, R. A., K. E. Fogarty, et al. Calcium gradients underlying polarization and chemotaxis of eosinophils. Science 254(5032):703–706, 1991.

    Article  Google Scholar 

  8. Cardoso, L., B. C. Herman, et al. Osteocyte apoptosis controls activation of intracortical resorption in response to bone fatigue. J. Bone Miner. Res. 24:597–605, 2008.

    Article  Google Scholar 

  9. Chandran, P., A. Sasidharan, et al. Highly biocompatible TiO(2):Gd(3)(+) nano-contrast agent with enhanced longitudinal relaxivity for targeted cancer imaging. Nanoscale 3(10):4150–4161, 2011.

    Article  Google Scholar 

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

    Article  MathSciNet  Google Scholar 

  11. Fahlgren, A., M. P. G. Bostrom, et al. Fluid pressure and flow as a cause of bone resorption. Acta Orthop. 81(4):508–516, 2010.

    Article  Google Scholar 

  12. Gardinier, J. D., C. W. Townend, et al. In situ permeability measurement of the mammalian lacunar-canalicular system. Bone 46(4):1075–1081, 2010.

    Article  Google Scholar 

  13. Hadjidakis, D. J., and I. I. Androulakis. Bone remodeling. Ann. NY Acad. Sci. 1092:385–396, 2006.

    Article  Google Scholar 

  14. He, S., Y. Su, et al. Some basic questions on mechanosensing in cell-substrate interaction. J. Mech. Phys. Solids 70:116–135, 2014.

    Article  MathSciNet  Google Scholar 

  15. Herman, B. C., L. Cardoso, et al. Activation of bone remodeling after fatigue: differential response to linear microcracks and diffuse damage. Bone 47(4):766–772, 2010.

    Article  Google Scholar 

  16. Ishii, M., J. Kikuta, et al. Chemorepulsion by blood S1P regulates osteoclast precursor mobilization and bone remodeling in vivo. J. Exp. Med. 207(13):2793–2798, 2010.

    Article  Google Scholar 

  17. Johansson, L., U. Edlund, et al. Bone resorption induced by fluid flow. J. Biomech. Eng. 131(9):094505, 2009.

    Article  Google Scholar 

  18. Kennedy, O. D., B. C. Herman, et al. Activation of resorption in fatigue-loaded bone involves both apoptosis and active pro-osteoclastogenic signaling by distinct osteocyte populations. Bone 50(5):1115–1122, 2012.

    Article  Google Scholar 

  19. Kikuta, J., S. Kawamura, et al. Sphingosine-1-phosphate-mediated osteoclast precursor monocyte migration is a critical point of control in antibone-resorptive action of active vitamin D. Proc. Natl. Acad. Sci. USA 110(17):7009–7013, 2013.

  20. Kim, S. Y., S. H. Park, et al. Mechanical stimulation and the presence of neighboring cells greatly affect migration of human mesenchymal stem cells. Biotechnol. Lett. 35(11):1817–1822, 2013.

    Article  Google Scholar 

  21. Koizumi, K., Y. Saitoh, et al. Role of CX3CL1/fractalkine in osteoclast differentiation and bone resorption. J. Immunol. 183(12):7825–7831, 2009.

    Article  Google Scholar 

  22. Kong, D., B. H. Ji, et al. Stabilizing to disruptive transition of focal adhesion response to mechanical forces. J. Biomech. 43(13):2524–2529, 2010.

    Article  Google Scholar 

  23. Li, P., M. Hu, et al. Fluid flow-induced calcium response in early or late differentiated osteoclasts. Ann. Biomed. Eng. 40(9):1874–1883, 2012.

    Article  Google Scholar 

  24. Li, P., C. Liu, et al. Fluid flow-induced calcium response in osteoclasts: signaling pathways. Ann. Biomed. Eng. 42(6):1250–1260, 2014.

    Article  Google Scholar 

  25. Liu, Y., L. Li, et al. Effects of fluid shear stress on bone resorption in rat osteoclasts. J. Biomech. Eng. 24(3):544–548, 2007.

    Google Scholar 

  26. Masuyama, R., J. Vriens, et al. TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts. Cell Metab. 8(3):257–265, 2008.

    Article  Google Scholar 

  27. Polacheck, W. J., J. L. Charest, et al. Interstitial flow influences direction of tumor cell migration through competing mechanisms. Proc. Natl. Acad. Sci. USA 108(27):11115–11120, 2011.

    Article  Google Scholar 

  28. Schwab, A., F. Finsterwalder, et al. Intracellular Ca2+ distribution in migrating transformed epithelial cells. Pflugers Arch. 434(1):70–76, 1997.

    Article  Google Scholar 

  29. Sheikh, S., G. E. Rainger, et al. Exposure to fluid shear stress modulates the ability of endothelial cells to recruit neutrophils in response to tumor necrosis factor-alpha: a basis for local variations in vascular sensitivity to inflammation. Blood 102(8):2828–2834, 2003.

  30. Shiu, Y. T., S. Li, et al. Rho mediates the shear-enhancement of endothelial cell migration and traction force generation. Biophys. J. 86(4):2558–2565, 2004.

    Article  Google Scholar 

  31. Teitelbaum, S. L. Bone resorption by osteoclasts. Science 289(5484):1504–1508, 2000.

    Article  Google Scholar 

  32. Thompson, W. R., C. T. Rubin, et al. Mechanical regulation of signaling pathways in bone. Gene 503(2):179–193, 2012.

    Article  Google Scholar 

  33. Tsuzuki, T., K. Okabe, et al. Osmotic membrane stretch increases cytosolic Ca(2+) and inhibits bone resorption activity in rat osteoclasts. Jpn. J. Physiol. 50(1):67–76, 2000.

    Article  Google Scholar 

  34. Waldorff, E. I., K. B. Christenson, et al. Microdamage repair and remodeling requires mechanical loading. J. Bone Miner. Res. 25(4):734–745, 2010.

    Google Scholar 

  35. Wang, H., W. Sun, et al. Polycystin-1 mediates mechanical strain-induced osteoblastic mechanoresponses via potentiation of intracellular calcium and Akt/beta-catenin pathway. PLoS One 9(3):e91730, 2014.

    Article  Google Scholar 

  36. Wang, L., T. Ye, et al. Repair of microdamage in osteonal cortical bone adjacent to bone screw. PLoS One 9(2):e89343, 2014.

    Article  Google Scholar 

  37. Wei, C., X. Wang, et al. Calcium flickers steer cell migration. Nature 457(7231):901–905, 2009.

    Article  Google Scholar 

  38. Weinbaum, S., S. C. Cowin, et al. A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J. Biomech. 27(3):339–360, 1994.

  39. Wheal, B. D., R. J. Beach, et al. Subcellular elevation of cytosolic free calcium is required for osteoclast migration. J. Bone Miner. Res. 29(3):725–734, 2014.

    Article  Google Scholar 

  40. Wiebe, S. H., S. M. Sims, et al. Calcium signalling via multiple P2 purinoceptor subtypes in rat osteoclasts. Cell. Physiol. Biochem. 9(6):323–337, 1999.

    Article  Google Scholar 

  41. Xia, S. L., and J. Ferrier. Calcium signal induced by mechanical perturbation of osteoclasts. J. Cell. Physiol. 163(3):493–501, 1995.

    Article  Google Scholar 

  42. Xia, S. L., and J. Ferrier. Localized calcium signaling in multinucleated osteoclasts. J. Cell. Physiol. 167(1):148–155, 1996.

    Article  Google Scholar 

  43. Zhong, Y., and B. Ji. How do cells produce and regulate the driving force in the process of migration? Eur. Phys. J. Spec. Top. 223(7):1373–1390, 2014.

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China [11372043 (BH), 11025208, 11372042, and 11221202 (BJ)] and the Fundamental Research Funds for the Central Universities [GZ2013015101 (BH)].

Conflict of interest

Chenglin Liu, Shuna Li, Baohua Ji, and Bo Huo declare that they have no conflicts of interest.

Ethical Standards

No human or animal studies were carried out by the authors for this article.

Author information

Authors and Affiliations

  1. Biomechanics and Biomaterials Laboratory, Department of Mechanics, School of Aerospace Engineering, Beijing Institute of Technology, No. 5 South Zhongguancun Street, Beijing, 100081, People’s Republic of China

    Chenglin Liu, Shuna Li, Baohua Ji & Bo Huo

Authors
  1. Chenglin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shuna Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Baohua Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bo Huo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Baohua Ji or Bo Huo.

Additional information

Associate Editor Daniel Fletcher oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, C., Li, S., Ji, B. et al. Flow-Induced Migration of Osteoclasts and Regulations of Calcium Signaling Pathways. Cel. Mol. Bioeng. 8, 213–223 (2015). https://doi.org/10.1007/s12195-014-0372-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12195-014-0372-5

Keywords

Search

Navigation