Downloads: 101
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
eLife.71931.pdf | 2.33 MB | Adobe PDF | View/Open |
Title: | C-type natriuretic peptide facilitates autonomic Ca²⁺ entry in growth plate chondrocytes for stimulating bone growth |
Authors: | Miyazaki, Yuu Ichimura, Atsuhiko https://orcid.org/0000-0003-0366-5211 (unconfirmed) Kitayama, Ryo Okamoto, Naoki Yasue, Tomoki Liu, Feng Kawabe, Takaaki Nagatomo, Hiroki Ueda, Yohei Yamauchi, Ichiro https://orcid.org/0000-0002-4236-502X (unconfirmed) Hakata, Takuro Nakao, Kazumasa Kakizawa, Sho https://orcid.org/0000-0001-8396-5411 (unconfirmed) Nishi, Miyuki Mori, Yasuo Akiyama, Haruhiko Nakao, Kazuwa Takeshima, Hiroshi 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 |
Appears in Collections: | Journal Articles |
This item is licensed under a Creative Commons License