title: Osteoblastic differentiation enhances expression of TRPV4 that is required for calcium oscillation induced by mechanical force.
abstract: Mechanical stress is known to alter bone mass and the loss of force stimuli leads to reduction of bone mass. However, molecules involved in this phenomenon are incompletely understood. As mechanical force would affect signaling events in cells, we focused on a calcium channel, TRPV4 regarding its role in the effects of force stimuli on calcium in osteoblasts. TRPV4 expression levels were enhanced upon differentiation of osteoblasts in culture. We found that BMP-2 treatment enhanced TRPV4 gene expression in a dose dependent manner. BMP-2 effects on TRPV4 expression were suppressed by inhibitors for transcription and new protein synthesis. In these osteoblasts, a TRPV4-selective agonist, 4α-PDD, enhanced calcium signaling and the effects of 4α-PDD were enhanced in differentiated osteoblasts compared to the control cells. Fluid flow, as a mechanical stimulation, induced intracellular calcium oscillation in wild type osteoblasts. In contrast, TRPV4 deficiency suppressed calcium oscillation significantly even when the cells were subjected to fluid flow. These data suggest that TRPV4 is involved in the flow-induced calcium signaling in osteoblasts.
authors: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
authors: Takafumi
authors: T
authors: Suzuki
authors: Takuya
authors: T
authors: Notomi
authors: Daisuke
authors: D
authors: Miyajima
authors: Fumitaka
authors: F
authors: Mizoguchi
authors: Tadayoshi
authors: T
authors: Hayata
authors: Tetsuya
authors: T
authors: Nakamoto
authors: Ryo
authors: R
authors: Hanyu
authors: Paksinee
authors: P
authors: Kamolratanakul
authors: Atsuko
authors: A
authors: Mizuno
authors: Makoto
authors: M
authors: Suzuki
authors: Yoichi
authors: Y
authors: Ezura
authors: Yuichi
authors: Y
authors: Izumi
authors: Masaki
authors: M
authors: Noda
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012212:Rheology / Q000187:drug effects; D013314:Stress, Mechanical; D050916:TRPV Cation Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D055396:Bone Morphogenetic Protein 2; D003470:Culture Media; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse