論文

査読有り 国際誌
2022年3月15日

C-type natriuretic peptide facilitates autonomic Ca2+ entry in growth plate chondrocytes for stimulating bone growth

eLife
  • Yuu Miyazaki
  • Atsuhiko Ichimura
  • Ryo Kitayama
  • Naoki Okamoto
  • Tomoki Yasue
  • Feng Liu
  • Takaaki Kawabe
  • Hiroki Nagatomo
  • Yohei Ueda
  • Ichiro Yamauchi
  • Takuro Hakata
  • Kazumasa Nakao
  • Sho Kakizawa
  • Miyuki Nishi
  • Yasuo Mori
  • Haruhiko Akiyama
  • Kazuwa Nakao
  • Hiroshi Takeshima
  • 全て表示

11
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.7554/elife.71931
出版者・発行元
eLife Sciences Publications, Ltd

The growth plates are cartilage tissues found at both ends of developing bones, and vital proliferation and differentiation of growth plate chondrocytes are primarily responsible for bone growth. C-type natriuretic peptide (CNP) stimulates bone growth by activating natriuretic peptide receptor 2 (NPR2) which is equipped with guanylate cyclase on the cytoplasmic side, but its signaling pathway is unclear in growth plate chondrocytes. We previously reported that transient receptor potential melastatin-like 7 (TRPM7) channels mediate intermissive Ca2+ influx in growth plate chondrocytes, leading to activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) for promoting bone growth. In this report, we provide evidence from experiments using mutant mice, indicating a functional link between CNP and TRPM7 channels. Our pharmacological data suggest that CNP-evoked NPR2 activation elevates cellular cGMP content and stimulates big-conductance Ca2+-dependent K+ (BK) channels as a substrate for cGMP-dependent protein kinase (PKG). BK channel-induced hyperpolarization likely enhances the driving force of TRPM7-mediated Ca2+ entry and seems to accordingly activate CaMKII. Indeed, ex vivo organ culture analysis indicates that CNP-facilitated bone growth is abolished by chondrocyte-specific Trpm7 gene ablation. The defined CNP signaling pathway, the NPR2-PKG-BK channel–TRPM7 channel–CaMKII axis, likely pinpoints promising target proteins for developing new therapeutic treatments for divergent growth disorders.

リンク情報
DOI
https://doi.org/10.7554/elife.71931
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/35287796
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923661
URL
https://cdn.elifesciences.org/articles/71931/elife-71931-v1.pdf
URL
https://cdn.elifesciences.org/articles/71931/elife-71931-v1.xml
ID情報
  • DOI : 10.7554/elife.71931
  • eISSN : 2050-084X
  • PubMed ID : 35287796
  • PubMed Central 記事ID : PMC8923661

エクスポート
BibTeX RIS