Transient receptor potential vanilloid 4 deficiency suppresses unloading-induced bone loss

被引：93

作者：

Mizoguchi, Fumitaka ^{[1
,2
,3
]}

Mizuno, Atsuko

Hayata, Tadayoshi ^{[1
]}

Nakashima, Kazuhisa ^{[1
,2
]}

Heller, Stefan ^{[4
]}

Ushida, Takashi ^{[5
]}

Sokabe, Masahiro ^{[6
]}

Miyasaka, Nobuyuki ^{[2
,3
]}

Suzuki, Makoto

Ezurai, Yoichi ^{[1
,7
]}

Noda, Masaki ^{[1
,2
,7
]}

机构：

[1] Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Chiyoda Ku, Tokyo 1010062, Japan

[2] 21st Century Ctr Excellence COE Program Frontier, Tokyo, Japan

[3] Tokyo Med & Dent Univ, Grad Sch, Dept Med & Rheumatol, Tokyo 1010062, Japan

[4] Stanford Univ, Sch Med, Dept Otolaryngol Head & Neck Surg & Mol & Cellula, Stanford, CA 94305 USA

[5] Univ Tokyo, Sch Med, Ctr Dis Biol & Integrat Med, Tokyo 113, Japan

[6] Nagoya Univ, Grad Sch Med, Dept Physiol, Nagoya, Aichi 4648601, Japan

[7] Tokyo Med & Dent Univ, Hard Tissue Genome Res Ctr, Tokyo 1010062, Japan

来源：

JOURNAL OF CELLULAR PHYSIOLOGY | 2008年 / 216卷 / 01期

关键词：

D O I：

10.1002/jcp.21374

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：47 / 53

页数：7

共 43 条

[1] A capsaicin-receptor homologue with a high threshold for noxious heat [J].