Transient receptor potential vanilloid 1 and 4 double knockout leads to increased bone mass in mice

被引：17

作者：

Nishimura, Haruki ^{[1
]}

Kawasaki, Makoto ^{[1
]}

Tsukamoto, Manabu ^{[1
]}

Menuki, Kunitaka ^{[1
]}

Suzuki, Hitoshi ^{[1
]}

Matsuura, Takanori ^{[1
]}

Baba, Kazuhiko ^{[1
]}

Motojima, Yasuhito ^{[1
]}

Fujitani, Teruaki ^{[1
]}

Ohnishi, Hideo ^{[1
]}

Yamanaka, Yoshiaki ^{[1
]}

Kosugi, Kenji ^{[1
]}

Okada, Yasuaki ^{[1
]}

Tokuda, Kotaro ^{[1
]}

Tajima, Takafumi ^{[1
]}

Yoshioka, Toru ^{[2
]}

Okimoto, Nobukazu ^{[3
]}

Ueta, Yoichi ^{[4
]}

Sakai, Akinori ^{[1
]}

机构：

[1] Univ Occupat & Environm Hlth, Sch Med, Dept Orthopaed Surg, Yahatanishi Ku, 1-1 Iseigaoka, Kitakyushu, Fukuoka 8078555, Japan

[2] Shimura Hosp, Dept Orthopaed, Naka Ku, 3-13 Funairimachi, Hiroshima 7300841, Japan

[3] Okimoto Clin, 185-4 Yutakamachikubi, Kure, Hiroshima 7340304, Japan

[4] Univ Occupat & Environm Hlth, Sch Med, Dept Physiol, Yahatanishi Ku, 1-1 Iseigaoka, Kitakyushu, Fukuoka 8078555, Japan

来源：

BONE REPORTS | 2020年 / 12卷

基金：

日本学术振兴会;

关键词：

Transient receptor potential vanilloid; Micro-CT; Bone histomorphometry; Cell culture; Osteogenesis; Preosteoclast; MINERAL DENSITY; MARROW CAPACITY; TRPV4; EXPRESSION; DIFFERENTIATION; TURNOVER; CELLS; BODY; FAT; DISRUPTION;

D O I：

10.1016/j.bonr.2020.100268

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Calcium balance is important in bone homeostasis. The transient receptor potential vanilloid (TRPV) channel is a nonselective cation channel permeable to calcium and is activated by various physiological and pharmacological stimuli. TRPV1 and TRPV4, in particular, have important roles in intracellular Ca2+ signaling and extracellular calcium homeostasis in bone cells. TRPV1 and TRPV4 separately mediate osteoclast and osteoblast differentiation, and deficiency in any of these channels leads to increased bone mass. However, it remains unknown whether bone mass increases in the absence of both TRPV1 and TRPV4. In this study, we used TRPV1 and TRPV4 double knockout (DKO) mice to evaluate their bone mass in vivo, and osteoclast and osteoblast differentiation in vitro. Our results showed that DKO mice and wild type (WT) mice had no significant difference in body weight and femur length. However, the results of dual-energy X-ray absorption, microcomputed tomography, and bone histomorphometry clearly showed that DKO mice had higher bone mass than WT mice. Furthermore, DKO mice had less multinucleated osteoclasts and had lower bone resorption. In addition, the results of cell culture using flushed bone marrow from mouse femurs and tibias showed that osteoclast differentiation was suppressed, whereas osteoblast differentiation was promoted in DKO mice. In conclusion, our results suggest that the increase in bone mass in DKO mice was induced not only by the suppression of osteoclast differentiation and activity but also by the augmentation of osteoblast differentiation and activity. Our findings reveal that both the single deficiency of TRPVs and the concurrent deficiency of TRPVs result in an increase in bone mass. Furthermore, our data showed that DKO mice and single KO mice had varying approaches to osteoclast and osteoblast differentiation in vitro, and therefore, it is important to conduct further studies on TRPVs regarding the increase in bone mass to explore not only individual but also a combination of TRPVs.

引用

页数：10

共 49 条

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