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Title: C-type natriuretic peptide facilitates autonomic Ca²⁺ entry in growth plate chondrocytes for stimulating bone growth
Authors: Miyazaki, Yuu
Ichimura, Atsuhiko  KAKEN_id  orcid https://orcid.org/0000-0003-0366-5211 (unconfirmed)
Kitayama, Ryo
Okamoto, Naoki
Yasue, Tomoki
Liu, Feng
Kawabe, Takaaki
Nagatomo, Hiroki
Ueda, Yohei  kyouindb  KAKEN_id
Yamauchi, Ichiro  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-4236-502X (unconfirmed)
Hakata, Takuro
Nakao, Kazumasa
Kakizawa, Sho  KAKEN_id  orcid https://orcid.org/0000-0001-8396-5411 (unconfirmed)
Nishi, Miyuki
Mori, Yasuo  kyouindb  KAKEN_id
Akiyama, Haruhiko
Nakao, Kazuwa
Takeshima, Hiroshi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-4525-3725 (unconfirmed)
Author's alias: 宮崎, 侑
市村, 敦彦
北山, 諒
岡本, 直樹
安江, 智生
劉, 楓
川邊, 隆彰
長友, 宏樹
植田, 洋平
山内, 一郎
伯田, 琢郎
中尾, 一祐
柿澤, 昌
西, 美幸
森, 泰生
秋山, 治彦
中尾, 一和
竹島, 浩
Keywords: Research Article
Cell Biology
bone development
Ca²⁺ influx
chondrogenesis
membrane potential
natriuretic peptide receptor 2
TRPM7 channel
Mouse
Issue Date: 2022
Publisher: eLife Sciences Publications, Ltd
Journal title: eLife
Volume: 11
Thesis number: e71931
Abstract: 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.
Description: 骨を長く伸ばす仕組みの一端を解明 --C型ナトリウム利尿ペプチド(CNP)は軟骨細胞内Ca2+シグナルを活性化して骨伸長を促す--. 京都大学プレスリリース. 2022-03-16.
Pumping calcium for bigger bones: New intracellular signaling mechanism discovered for long bone growth. 京都大学プレスリリース. 2022-05-13.
Rights: © 2022, Miyazaki et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
URI: http://hdl.handle.net/2433/268928
DOI(Published Version): 10.7554/eLife.71931
PubMed ID: 35287796
Related Link: https://www.kyoto-u.ac.jp/ja/research-news/2022-03-16
https://www.kyoto-u.ac.jp/en/research-news/2022-05-13-1
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