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A Lab-On-A-Chip Platform for Stimulating Osteocyte Mechanotransduction and Analyzing Functional Outcomes of Bone Remodeling
Published on: May 21, 2020
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Cx43 and mechanotransduction in bone.
Lilian I Plotkin1, Toni L Speacht, Henry J Donahue
1Department of Anatomy and Cell Biology, Indiana University School of Medicine, and Roudebush Veterans Administration Medical Center, 635 Barnhill Drive, MS-5035, Indianapolis, IN, 46202, USA, lplotkin@iupui.edu.
Current Osteoporosis Reports
|January 25, 2015
Summary
Connexin 43 (Cx43) channels in bone cells are not required for mechanical adaptation. Instead, Cx43 mediates negative consequences when mechanical stimuli are absent, impacting bone mass regulation.
Area of Science:
- Bone Biology
- Mechanobiology
- Cellular Physiology
Background:
- Bone mass is regulated by osteoblasts and osteoclasts, coordinated by osteocytes sensing mechanical forces.
- Connexin 43 (Cx43) channels in osteoblasts and osteocytes are implicated in bone mass control and mechanotransduction.
- Cx43 hemichannels are activated by fluid flow and protect cells from apoptosis during mechanical stimulation in vitro.
Purpose of the Study:
- To investigate the role of Cx43 in osteoblasts and osteocytes in bone's response to mechanical loading and unloading.
- To elucidate the specific contribution of Cx43 channels to bone adaptation mechanisms.
Main Methods:
- Utilizing mouse models with targeted deletions of Cx43 in osteoblasts and/or osteocytes.
- Assessing bone anabolic and catabolic responses to mechanical loading and unloading in these genetically modified mice.
Main Results:
- Mice lacking Cx43 in osteoblasts and/or osteocytes exhibited an exaggerated anabolic response to mechanical loading.
- Conversely, these mice demonstrated a reduced catabolic response when subjected to unloading.
- These findings suggest Cx43 channels are not essential for sensing mechanical stimuli but mediate negative outcomes in their absence.
Conclusions:
- Cx43 channels in osteoblastic cells are dispensable for mediating the direct response to mechanical stimulation.
- Cx43 appears to play a crucial role in regulating bone's response to the *lack* of mechanical stimuli.
- The precise molecular mechanisms underlying these unexpected Cx43-dependent responses to mechanical unloading require further investigation.
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