Transient receptor potential vanilloid 4 deficiency suppresses unloading-induced bone loss
Transient receptor potential vanilloid 4 deficiency suppresses unloading-induced bone loss
复制标题
DOI：
10.1002/jcp.21374
复制
发表时间：
2008-07-01
影响因子：
5.6
通讯作者：
Noda, Masaki
中科院分区：
文献类型：
--
作者：
Mizoguchi, Fumitaka;Mizuno, Atsuko;Noda, Masaki
机械感知是生物事件的重要组成部分之一。在骨中，如在卧床患者的卸载诱导的骨质疏松症中所观察到的，机械应力决定了骨量的水平。许多分子已被认为参与感知骨中的机械应力，而这一事件的完整途径尚未确定。我们研究了TRPV4在卸载诱导的骨丢失中的作用。后肢去负荷诱导野生型小鼠骨质减少。相反，TRPV4缺乏抑制这种卸载诱导的骨丢失。作为这种作用的潜在机制，TRPV4缺乏抑制了卸载诱导的矿物质沉积率和骨形成率水平的降低。在这些小鼠中，TRPV 4缺乏抑制了卸载诱导的初级骨小梁中破骨细胞数量的增加。TRPV4缺乏也抑制了卸载引起的原发性骨小梁纵向长度的减少。TRPV4蛋白在成骨细胞和破骨细胞中都有表达。这些结果表明TRPV4在卸载诱导的骨丢失中起关键作用。
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.