Transient receptor potential vanilloid 4 deficiency suppresses unloading-induced bone loss.
Mechanosensing is one of the crucial components of the biological events. In bone, as observed in unloading-induced osteoporosis in bed ridden patients, mechanical stress determines the levels of bone mass. Many molecules have been suggested to be involved in sensing mechanical stress in bone, while the full pathways for this event has not yet been identified. We examined the role of TRPV4 in unloading-induced bone loss. Hind limb unloading induced osteopenia in wild-type mice. In contrast, TRPV4 deficiency suppressed such unloading-induced bone loss. As underlying mechanism for such effects, TRPV4 deficiency suppressed unloading-induced reduction in the levels of mineral apposition rate and bone formation rate. In these mice, unloading-induced increase in the number of osteoclasts in the primary trabecular bone was suppressed by TRPV4 deficiency. Unloading-induced reduction in the longitudinal length of primary trabecular bone was also suppressed by TRPV4 deficiency. TRPV4 protein is expressed in both osteoblasts and osteoclasts. These results indicated that TRPV4 plays a critical role in unloading-induced bone loss.
Mizoguchi
Fumitaka
F
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Mizuno
Atsuko
A
Hayata
Tadayoshi
T
Nakashima
Kazuhisa
K
Heller
Stefan
S
Ushida
Takashi
T
Sokabe
Masahiro
M
Miyasaka
Nobuyuki
N
Suzuki
Makoto
M
Ezura
Yoichi
Y
Noda
Masaki
M
D016475:3T3 Cells; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D019417:Hindlimb Suspension / Q000009:adverse effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D011897:Random Allocation; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse