Knockout of TRPV6 Causes Osteopenia in Mice by Increasing Osteoclastic Differentiation and Activity

Cellular Physiology and Biochemistry

关键词: TRPV6;    Ca2+;    Osteoclastogenesis;    Bone resorption;   

DOI  :  10.1159/000358653

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background Calcium ion (Ca²⁺) signals are required for osteoclast differentiation. Previous study showed that transient receptor potential vanilloid 5 (TRPV5) is an essential Ca²⁺ transporter in osteoclastogenesis and bone resorption. TRPV5 and TRPV6 represent two highly homologous members within the transient receptor potential (TRP) superfamily. However, the role of TRPV6 in bone metabolism is still controversial and little is known about the involvement of TRPV6 in receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclastogenesis. Methods In our study, gene knockout mice, RNA interference, western blot, quantitative real-time PCR, tartrate-resistant acid phosphatase (TRAP) staining, pit formation assay, histomorphometry and measurement of serum parameters were employed to investigate the role of TRPV6 in bone homeostasis, osteoclastogenesis and bone resorption. Results We found that TRPV6 depletion results in noticeable destruction of bone microarchitecture in TRPV6 knockout mice (TRPV6^-/-), suggesting that TRPV6 is a critical regulator in bone homeostasis. Inactivation of Trpv6 had no effect on osteoblastic bone formation. However, quantification of the TRAP staining showed a significantly increased osteoclast number and surface area in the metaphyseal area of femurs bone sections derived from TRPV6^-/- mice. In agreement with our observations from TRPV6^-/- mice, TRPV6 depletion in vitro significantly increased osteoclasts differentiation and bone resorption activity. Conclusion Based on these results above, we can draw conclusions that TRPV6 plays an essential role in bone metabolism and is a critical regulator in osteoclasts differentiation and bone resorption.

【 授权许可】

CC BY-NC-ND