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Transient receptor potential vanilloid 1 and 4 double knockout leads to increased bone mass in mice
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 intracellul...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191598/ https://www.ncbi.nlm.nih.gov/pubmed/32373678 http://dx.doi.org/10.1016/j.bonr.2020.100268 |
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author | Nishimura, Haruki Kawasaki, Makoto Tsukamoto, Manabu Menuki, Kunitaka Suzuki, Hitoshi Matsuura, Takanori Baba, Kazuhiko Motojima, Yasuhito Fujitani, Teruaki Ohnishi, Hideo Yamanaka, Yoshiaki Kosugi, Kenji Okada, Yasuaki Tokuda, Kotaro Tajima, Takafumi Yoshioka, Toru Okimoto, Nobukazu Ueta, Yoichi Sakai, Akinori |
author_facet | Nishimura, Haruki Kawasaki, Makoto Tsukamoto, Manabu Menuki, Kunitaka Suzuki, Hitoshi Matsuura, Takanori Baba, Kazuhiko Motojima, Yasuhito Fujitani, Teruaki Ohnishi, Hideo Yamanaka, Yoshiaki Kosugi, Kenji Okada, Yasuaki Tokuda, Kotaro Tajima, Takafumi Yoshioka, Toru Okimoto, Nobukazu Ueta, Yoichi Sakai, Akinori |
author_sort | Nishimura, Haruki |
collection | PubMed |
description | 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 Ca(2+) 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. |
format | Online Article Text |
id | pubmed-7191598 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-71915982020-05-05 Transient receptor potential vanilloid 1 and 4 double knockout leads to increased bone mass in mice Nishimura, Haruki Kawasaki, Makoto Tsukamoto, Manabu Menuki, Kunitaka Suzuki, Hitoshi Matsuura, Takanori Baba, Kazuhiko Motojima, Yasuhito Fujitani, Teruaki Ohnishi, Hideo Yamanaka, Yoshiaki Kosugi, Kenji Okada, Yasuaki Tokuda, Kotaro Tajima, Takafumi Yoshioka, Toru Okimoto, Nobukazu Ueta, Yoichi Sakai, Akinori Bone Rep Article 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 Ca(2+) 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. Elsevier 2020-04-23 /pmc/articles/PMC7191598/ /pubmed/32373678 http://dx.doi.org/10.1016/j.bonr.2020.100268 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nishimura, Haruki Kawasaki, Makoto Tsukamoto, Manabu Menuki, Kunitaka Suzuki, Hitoshi Matsuura, Takanori Baba, Kazuhiko Motojima, Yasuhito Fujitani, Teruaki Ohnishi, Hideo Yamanaka, Yoshiaki Kosugi, Kenji Okada, Yasuaki Tokuda, Kotaro Tajima, Takafumi Yoshioka, Toru Okimoto, Nobukazu Ueta, Yoichi Sakai, Akinori Transient receptor potential vanilloid 1 and 4 double knockout leads to increased bone mass in mice |
title | Transient receptor potential vanilloid 1 and 4 double knockout leads to increased bone mass in mice |
title_full | Transient receptor potential vanilloid 1 and 4 double knockout leads to increased bone mass in mice |
title_fullStr | Transient receptor potential vanilloid 1 and 4 double knockout leads to increased bone mass in mice |
title_full_unstemmed | Transient receptor potential vanilloid 1 and 4 double knockout leads to increased bone mass in mice |
title_short | Transient receptor potential vanilloid 1 and 4 double knockout leads to increased bone mass in mice |
title_sort | transient receptor potential vanilloid 1 and 4 double knockout leads to increased bone mass in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191598/ https://www.ncbi.nlm.nih.gov/pubmed/32373678 http://dx.doi.org/10.1016/j.bonr.2020.100268 |
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