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Role of pannexin 1 channels in load‐induced skeletal response
Author(s) -
SerefFerlengez Zeynep,
UrbanMaldonado Marcia,
Sun Hui B.,
Schaffler Mitchell B.,
Suadicani Sylvia O.,
Thi Mia M.
Publication year - 2019
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.13914
Subject(s) - mechanosensitive channels , pannexin , osteocyte , microbiology and biotechnology , wnt signaling pathway , sclerostin , signal transduction , mechanotransduction , biology , chemistry , anatomy , receptor , ion channel , in vitro , gap junction , osteoblast , biochemistry , intracellular , connexin
The pannexin 1 (Panx1) channel is a mechanosensitive channel that interacts with P2X7 receptors (P2X7R) to form a functional complex that has been shown in vitro to play an essential role in osteocyte mechanosignaling. While the participation of P2X7R in skeletal responses to mechanical loading has been demonstrated, the role of Panx1 and its interplay with P2X7R still remain to be determined. In this study, we use a global Panx1 −/− mouse model and in vivo mechanical loading to demonstrate that Panx1 channels play an essential role in load‐induced skeletal responses. We found that absence of Panx1 not only disrupts the P2X7R–Panx1 signaling complex, but also alters load‐induced regulation of P2X7R expression. Moreover, lack of Panx1 completely abolished load‐induced periosteal bone formation. Load‐induced regulation of β‐catenin and sclerostin expression was dysregulated in Panx1 −/− , compared to wild‐type, bone. This finding suggests that Panx1 deficiency disrupts Wnt/β‐catenin signaling by lowering β‐catenin while favoring inhibition of bone formation by increasing load‐induced sclerostin expression. This study demonstrates the existence of a Panx1‐dependent mechanosensitive mechanism that not only modulates ATP signaling but also coordinates Wnt/β‐catenin signaling that is essential for proper skeletal response to mechanical loading.