Connexin 43 Channels in Osteocytes Regulate Bone Responses to Mechanical Unloading

Frontiers in Physiology

Jean X. Jiang¹  Peng Shang²  Dezhi Zhao³  Meng Chen³  Guobin Li³  Ruofei Liu³  Huiyun Xu⁴  Hui Yang⁴ 

[1] Department of Biochemistry and Structural Biology, The University of Texas Health Science Center, San Antonio, TX, United States;Key Laboratory for Space Bioscience and Biotechnology, Research and Development Institute in Shenzhen, Northwestern Polytechnical University, Shenzhen, China;Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China;Research Center of Special Environmental Biomechanics and Medical Engineering, Northwestern Polytechnical University, Xi’an, China;

关键词: Cx43;    gap junction;    hemichannel;    hindlimb unloading;    osteocyte;   

DOI  :  10.3389/fphys.2020.00299

来源: DOAJ

【 摘 要 】

Connexin (Cx) 43 forms gap junctions and hemichannels that mediate communication between osteocytes and adjacent cells or the extracellular environment in bone, respectively. To investigate the role of each channel type in response to mechanical unloading, two transgenic mouse models overexpressing dominant-negative Cx43 predominantly in osteocytes driven by a 10 kb dentin matrix protein 1 (Dmp1) promoter were generated. The R76W mutation resulted in gap junction inhibition and enhancement of hemichannels, whereas the Δ130–136 mutation inhibited both gap junctions and hemichannels. Both mutations led to cortical bone loss with increased endocortical osteoclast activity during unloading. Increased periosteal osteoclasts with decreased apoptotic osteocytes were observed only in R76W mice. These findings indicated that inhibiting osteocytic Cx43 channels promotes bone loss induced by unloading, mainly in the cortical area; moreover, hemichannels protect osteocytes against apoptosis and promote periosteal bone remodeling, whereas gap junctions modulate endocortical osteoclast activity in response to unloading.

【 授权许可】

Unknown