title: ClC-3 chloride channel functions as a mechanically sensitive channel in osteoblasts.
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.
authors.affiliation: a State Key Laboratory of Military Stomatology, Department of Oral Biology, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.|b State Key Laboratory of Military Stomatology, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Military Stomatology, Department of Oral Biology, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Military Stomatology, Department of Oral Biology, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Military Stomatology, Department of Oral Biology, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: c State Key Laboratory of Military Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Mao
authors.affiliation: a State Key Laboratory of Military Stomatology, Department of Oral Biology, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Duan
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007700:Kinetics; D055595:Mechanical Phenomena; D051379:Mice; D018613:Microscopy, Confocal; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D060449:Wnt Signaling Pathway
chemical_list: D015415:Biomarkers; D018118:Chloride Channels; C115376:ClC-3 channel; D050659:Core Binding Factor Alpha 1 Subunit; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C493716:Runx2 protein, mouse; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1
keywords: ClC-3; canaux chloriques; chloride channels; gene regulation; mechanical stimulation; osteodifferentiation; ostéo-différenciation; régulation génique; stimulation mécanique