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- Title
ClC-3 chloride channel functions as a mechanically sensitive channel in osteoblasts.
- Authors
Wang, Huan; Wang, Rong; Wang, Zhe; Liu, Qian; Mao, Yong; Duan, Xiaohong
- Abstract
Mechanical stimulation usually causes the volume changes of osteoblasts. Whether these volume changes could be sensed by the ClC-3 chloride channel, a volume-sensitive ion channel, and further promote the osteodifferentiation in osteoblasts has not been determined. In this study, we applied persistent static compression on MC3T3-E1 cells to detect the expression changes of ClC-3, osteogenic markers, as well as some molecules related with signaling transduction pathway. We tested the key role of ClC-3 in transferring the mechanical signal to osteoinduction by ClC-3 overexpressing and siRNA technique. We found that ClC-3 level was up-regulated by mechanical stimulation in MC3T3-E1 cells. Mechanical force also up-regulated the mRNA level of osteogenic markers such as alkaline phosphatase ( Alp), bone sialoprotein ( Bsp), and osteocalcin ( Oc), which could be blocked or strengthened by Clcn3 siRNA or overexpressing, and Alp expression was more sensitive to the changes of ClC-3 level. We also found that runt-related transcription factor 2 (Runx2), transforming growth factor beta 1 (TGF-β1), and Wnt pathway might be involved in ClC-3 mediated mechanical transduction in osteoblasts. The data from the current study suggest that the ClC-3 chloride channel acts as a mechanically sensitive channel to regulate osteodifferentiation in osteoblasts.
- Subjects
CHLORIDE channels; OSTEOBLASTS; CELL differentiation; SMALL interfering RNA; GENETIC overexpression
- Publication
Biochemistry & Cell Biology, 2015, Vol 93, Issue 6, p558
- ISSN
0829-8211
- Publication type
Article
- DOI
10.1139/bcb-2015-0018