Mechanosensitive piezo1 calcium channel activates connexin 43 hemichannels through PI3K signaling pathway in bone.
Mechanosensitive piezo1 calcium channel activates connexin 43 hemichannels through PI3K signaling pathway in bone.
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DOI：
10.1186/s13578-022-00929-w
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发表时间：
2022-12-01
影响因子：
7.5
通讯作者：
Jiang, Jean X.
中科院分区：
文献类型：
--
作者：
Zeng, Yan;Riquelme, Manuel A.;Hua, Rui;Zhang, Jingruo;Acosta, Francisca M.;Gu, Sumin;Jiang, Jean X.
机械负荷促进骨形成，骨细胞是骨中主要的机械感觉细胞。骨细胞中的Piezo 1通道和连接蛋白43半通道（Cx43 HCs）在机械负荷引起的机械传导和合成代谢功能中起重要作用。然而，涉及骨细胞和骨中Piezo 1通道和Cx43 HCs的机械转导机制仍然未知。我们发现，像机械负荷，Piezo 1特异性激动剂Yoda 1能够增加细胞内Ca 2+信号转导和激活Cx43 HC，而Yoda 1拮抗剂Dooku 1抑制Ca 2+和Cx43 HC激活诱导的机械负荷和Yoda 1。此外，Yoda 1激活的细胞内Ca 2+信号通过抑制Cx43 HC和泛连接蛋白1（Panx 1）通道以及ATP-P2 X受体信号传导而减少。Piezo 1和Cx43 HC共定位于骨细胞表面，Yoda 1激活的PI 3 K-Akt信号调节Cx43 HC的开放。此外，通过抑制体内Piezo 1激活，通过胫骨上的机械负荷来消融Cx43 HCs开放。我们证明，在机械应力下，由Piezo 1激活的细胞内Ca 2+增加通过PI 3 K-Akt调节HC的开放，并通过打开的Cx43 HC，沿着Panx 1通道，ATP-P2 X信号传导维持细胞内Ca 2+信号，导致骨合成代谢功能。在线版本包含补充材料，可通过10.1186/s13578-022-00929-w获得。
Mechanical loading promotes bone formation and osteocytes are a major mechanosensory cell in the bone. Both Piezo1 channels and connexin 43 hemichannels (Cx43 HCs) in osteocytes are important players in mechanotransduction and anabolic function by mechanical loading. However, the mechanism underlying mechanotransduction involving Piezo1 channels and Cx43 HCs in osteocytes and bone remains unknown. We showed that, like mechanical loading, Piezo1 specific agonist Yoda1 was able to increase intracellular Ca2+ signaling and activate Cx43 HCs, while Yoda1 antagonist Dooku1 inhibited Ca2+ and Cx43 HC activation induced by both mechanical loading and Yoda1. Moreover, the intracellular Ca2+ signal activated by Yoda1 was reduced by the inhibition of Cx43 HCs and pannexin1 (Panx1) channels, as well as ATP-P2X receptor signaling. Piezo1 and Cx43 HCs were co-localized on the osteocyte cell surface, and Yoda1-activated PI3K-Akt signaling regulated the opening of Cx43 HCs. Furthermore, Cx43 HCs opening by mechanical loading on tibias was ablated by inhibition of Piezo1 activation in vivo. We demonstrated that upon mechanical stress, increased intracellular Ca2+ activated by Piezo1 regulates the opening of HCs through PI3K-Akt and opened Cx43 HCs, along with Panx1 channels, and ATP-P2X signaling sustain the intracellular Ca2+ signal, leading to bone anabolic function. The online version contains supplementary material available at 10.1186/s13578-022-00929-w.
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影响因子：
4.1
作者：
Brown GN;Leong PL;Guo XE
通讯作者：
Guo XE
DOI：
10.1002/jbmr.2740
发表时间：
2016-04
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Cheung WY;Fritton JC;Morgan SA;Seref-Ferlengez Z;Basta-Pljakic J;Thi MM;Suadicani SO;Spray DC;Majeska RJ;Schaffler MB
通讯作者：
Schaffler MB
影响因子：
3.3
作者：
Cherian, PP;Siller-Jackson, AJ;Jiang, JX
通讯作者：
Jiang, JX
DOI：
10.1073/pnas.1009382107
发表时间：
2010-08-03
影响因子：
11.1
作者：
Burra, Sirisha;Nicolella, Daniel P.;Jiang, Jean X.
通讯作者：
Jiang, Jean X.
影响因子：
4
作者：
Batra, Nidhi;Riquelme, Manuel A.;Jiang, Jean X.
通讯作者：
Jiang, Jean X.