Annals of Biomedical Engineering

, Volume 40, Issue 9, pp 1874–1883 | Cite as

Fluid Flow-Induced Calcium Response in Early or Late Differentiated Osteoclasts

  • Ping Li
  • Man Hu
  • Shujin Sun
  • Yan Zhang
  • Yuxin Gao
  • Mian Long
  • Bo HuoEmail author
  • Ding ZhangEmail author


Intracellular calcium oscillation caused by receptor activator of nuclear factor kappa-B ligand has been demonstrated to promote the differentiation of osteoclasts. Osteoclasts are recruited on the surface of trabeculae, and are exposed to fluid flow caused by the deformation of the bone matrix. However, the roles of fluid shear stress (FSS) on calcium response during the differentiation process of osteoclasts are still unknown. In the current study, the formation of tartrate-resistant acid phosphatase-positive, multinucleated osteoclasts from RAW264.7 macrophage cells were induced by co-culturing them with the conditioned medium from MC3T3-E1 osteoblasts. The in situ observations showed a high correlation between the area and the nuclear number of osteoclasts. The cells were stimulated by FSS at different levels (1 or 10 dyne/cm2) before (0 day) or after being induced for 4 or 8 days. The mechanically-induced calcium response was recorded and analyzed. The results indicated a different property of calcium oscillation for the osteoclasts in different fusion stages (i.e., more calcium-responsive peaks appeared in small osteoclasts than those in the larger ones). The rates of calcium influx decreased and the time of recovery in osteoclast cytosol increased along with the fusion of osteoclasts. In addition, increasing the FSS level enhanced the calcium oscillation of osteoclasts at early induction (4 days). However, this effect was weakened at the late induction (8 days). The present work could help provide understanding regarding the mechanism of the involvement of calcium in mechanically induced bone remodeling.


Osteoclasts Fluid shear stress Calcium oscillation Induction time Differentiation 



This work was supported by the National Natural Science Foundation of China [30970707 (BH) and 31070829 (DZ)], the National Key Basic Research Foundation of China (2011CB710904), and the Knowledge Innovation Project of the CAS (KJCX2-YW-L08) (ML).

Conflict of interest

No conflict of interested is assigned to the manuscript.


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Copyright information

© Biomedical Engineering Society 2012

Authors and Affiliations

  1. 1.Department of Stomatology, Faculty of Surgery, Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingPeople’s Republic of China
  2. 2.Key Laboratory of Microgravity, Center for Biomechanics and BioengineeringInstitute of Mechanics, Chinese Academy of SciencesBeijingPeople’s Republic of China

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