RT Journal Article
SR Electronic
T1 Connexin Hemichannels with Prostaglandin Release in Anabolic Function of Bone to Mechanical Loading
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.15.464551
DO 10.1101/2021.10.15.464551
A1 Dezhi Zhao
A1 Manuel A. Riquelme
A1 Teja Guda
A1 Chao Tu
A1 Huiyun Xu
A1 Sumin Gu
A1 Jean X. Jiang
YR 2021
UL http://biorxiv.org/content/early/2021/10/16/2021.10.15.464551.abstract
AB Mechanical stimulation, such as physical exercise, is essential for bone formation and health. Here, we demonstrate the critical role of osteocytic Cx43 hemichannels in anabolic function of bone in response to mechanical loading. Two transgenic mouse models, R76W and Δ130-136, expressing dominant-negative Cx43 mutants in osteocytes were adopted. Mechanical loading of tibial bone increased cortical bone mass and mechanical properties in wild-type and gap junction-impaired R76W mice through increased PGE2, endosteal osteoblast activity, and decreased sclerostin. These anabolic responses were impeded in gap junction/hemichannel-impaired Δ130-136 mice and accompanied by increased endosteal osteoclast activity. Specific inhibition of Cx43 hemichannels by Cx43(M1) antibody suppressed PGE2 secretion and impeded loading-induced endosteal osteoblast activity, bone formation and anabolic gene expression. PGE2 administration rescued the osteogenic response to mechanical loading impeded by impaired hemichannels. Together, osteocytic Cx43 hemichannels could be a potential new therapeutic target for treating bone loss and osteoporosis.Competing Interest StatementThe authors have declared no competing interest.