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Published on: November 13, 2023
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Connexin 43 channels are essential for normal bone structure and osteocyte viability
Huiyun Xu1, Sumin Gu, Manuel A Riquelme
1School of Life Sciences, Northwestern Polytechnical University, Xian, China; Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Summary
Connexin 43 (Cx43) hemichannels are crucial for osteocyte survival and bone remodeling, while gap junction channels influence bone formation and resorption processes. This study clarifies Cx43
Area of Science:
- Bone Biology and Physiology
- Cellular Communication
- Skeletal Development
Background:
- Connexin 43 (Cx43) is vital for bone health, with its absence leading to impaired bone function and increased osteocyte apoptosis.
- Cx43 mediates intercellular communication through gap junction channels and cell-environment signaling via hemichannels.
Purpose of the Study:
- To investigate the distinct roles of Cx43 gap junction channels and hemichannels in osteocytes.
- To elucidate the specific functions of Cx43 in bone remodeling and osteocyte survival using transgenic mouse models.
Main Methods:
- Generation of two transgenic mouse models overexpressing dominant-negative Cx43 mutants (R76W and Δ130-136) under a DMP1 promoter.
- Assessment of bone structure and biomechanical properties using micro-computed tomography (µCT) and histological analysis.
- Evaluation of osteocyte apoptosis, osteoclast activity, and serum bone turnover markers.
Main Results:
- Mice with inhibited Cx43 hemichannel and gap junction function (Δ130-136) exhibited increased bone mineral density and cortical bone area.
- Increased osteocyte apoptosis and endocortical osteoclast surface were observed in Δ130-136 mice, alongside enhanced periosteal bone formation.
- Cx43 hemichannels appear dominant in regulating osteocyte survival and bone apposition, while gap junctions influence bone remodeling.
Conclusions:
- Osteocytic Cx43 hemichannels play a critical role in maintaining osteocyte viability and regulating endocortical resorption and periosteal bone formation.
- Cx43 gap junction communication is implicated in the broader processes of bone remodeling.
- Targeting specific Cx43 channel functions may offer therapeutic strategies for bone diseases.
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