STIM1 and TRPV4 Regulate Fluid Flow-induced Calcium Oscillation at Early and Late Stages of Osteoclast Differentiation
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Published on 2018 by


Graphical abstract: Schematic representation of the roles of STIM1 and TRPV4 in the FSS-induced calcium responses of OC-Es and OC-Ls, respectively. Highlights: Expression of STIM1 and TRPV4 depends on the differentiation stage of osteoclasts. Osteoclasts at early or late differentiation stage show different calcium response to FSS. STIM1 and TRPV4 serve as extracellular Ca2+ influx channels in early and late differentiation osteoclasts, respectively, under FSS simulation. Abstract: Bone resorption is mainly mediated by osteoclasts (OCs), whose formation and function are regulated by intracellular Ca 2+ oscillation. Our previous studies demonstrated that fluid shear stress (FSS) lead to Ca 2+ oscillation through mechanosensitive cation-selective channels. However, the specific channels responsible for this FSS-induced Ca 2+ oscillation remain unknown. In the present study, we examined the expression of several Ca 2+ channels in OCs, including STIM1, ORAI1, TRPV1, TRPV4, TRPV5, and TRPV6, by western blotting and reverse transcription-polymerase chain reaction. The results showed that STIM1 was highly expressed in early stage OCs, while TRPV4 was highly expressed in late stage OCs. We observed intracellular Ca 2+ responses in OCs that were mechanically stimulated by FSS. When we blocked STIM1-dependent store-operated Ca 2+ entry or inhibited TRPV4 using siRNA or drug inhibition, FSS-induced Ca 2+ oscillations were almost undetectable in early and late stage OCs, respectively. These results indicate that STIM1 and TRPV4 act as mechanical transduction channels for OCs during the early and late differentiation stages, respectively, suggesting that these calcium channel could serve as markers of osteoclastogenesis or bone resorption.
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