ECTS Abstracts (2015) 1 P167

Activation of Osmo-Mechanosensitive TRP Channels Facilitate Increase of Ca2+-Mediated RANKL Expression in Mouse Osteoblastic Cells

Yu-Mi Yang, Ga-Yeon Son & Dong Min Shin


Department of Oral Biology, Yonsei University College of Dentistry, Seoul, Republic of Korea.


Mechanical stress plays an important role in the regulation of bone turnover. However, the intracellular mechanisms of mechanical stress under osteoblast differentiation and proliferation are not well understood. In this study, we investigated the effects of osmo-mechanosensitive transient receptor potential (TRP) channels-induced calcium signalling in primary mouse osteoblasts and MC3T3-E1 cells. Hypotonic stress induced significant increases of RANKL mRNA expression but not OPG. In addition, hypotonic stress-induced increases of intracellular calcium concentration ([Ca2+]i) and RANKL expression persisted in the presence of non-specific Ca2+ channel blockers or Ca2+-free bath solution. Furthermore, we examined hypotonic stress-induced effects on agonists and antagonists of osmo-mechanosensitive TRP channels in order to determine the cellular mechanism of hypotonic stress-mediated increases on [Ca2+]i and RANKL. We found that antagonists of TRPV4 and TRPM3 decreased hypotonic stress-mediated increases on [Ca2+]i and protein expression levels of RANKL and NFATc1. We also identified that hypotonic stress-induced effects reduced by the genetic suppression of TRPV4 and TRPM3. Taken together, our results indicate that hypotonic stress activates the expression of RANKL and NFATc1 by [Ca2+]i increases through TRPV4 and TRPM3 in osteoblasts. These effects may be important for the differentiation and proliferation of bone cells on bone remodelling that are mediated via mechanosensitive TRP channels.

Disclosure: The authors declared no competing interests. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2012R1A2A1A01003487) and (MOE) (2012R1A1A2007673).

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