NDLI: Mechanosensitive piezo1 calcium channel activates connexin 43 hemichannels through PI3K signaling pathway in bone

Content Provider	Springer Nature : BioMed Central
Author	Zeng, Yan Riquelme, Manuel A. Hua, Rui Zhang, Jingruo Acosta, Francisca M. Gu, Sumin Jiang, Jean X.
Abstract	Background 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. Results 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. Conclusion 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.
Related Links	https://cellandbioscience.biomedcentral.com/counter/pdf/10.1186/s13578-022-00929-w.pdf
Ending Page	18
Page Count	18
Starting Page	1
File Format	HTM / HTML
ISSN	20453701
DOI	10.1186/s13578-022-00929-w
Journal	Cell & Bioscience
Issue Number	1
Volume Number	12
Language	English
Publisher	BioMed Central
Publisher Date	2022-12-01
Access Restriction	Open
Subject Keyword	Cell Biology Microbiology Stem Cells Neurobiology Proteomics Mechanical loading Piezo1 Cx43 hemichannels Ca2+ signal PI3K-Akt pathway
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology
Journal Impact Factor	6.1/2023
5-Year Journal Impact Factor	7/2023

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