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Review

The Role of Connexin Channels in the Response of Mechanical Loading and Unloading of Bone

1
Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229, USA
2
Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 1146; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21031146
Received: 2 January 2020 / Revised: 31 January 2020 / Accepted: 4 February 2020 / Published: 9 February 2020
The skeleton adapts to mechanical loading to promote bone formation and remodeling. While most bone cells are involved in mechanosensing, it is well accepted that osteocytes are the principal mechanosensory cells. The osteocyte cell body and processes are surrounded by a fluid-filled space, forming an extensive lacuno-canalicular network. The flow of interstitial fluid is a major stress-related factor that transmits mechanical stimulation to bone cells. The long dendritic processes of osteocytes form a gap junction channel network connecting not only neighboring osteocytes, but also cells on the bone surface, such as osteoblasts and osteoclasts. Mechanosensitive osteocytes also form hemichannels that mediate the communication between the cytoplasmic and extracellular microenvironment. This paper will discuss recent research progress regarding connexin (Cx)-forming gap junctions and hemichannels in osteocytes, osteoblasts, and other bone cells, including those richly expressing Cx43. We will then cover the recent progress regarding the regulation of these channels by mechanical loading and the role of integrins and signals in mediating Cx43 channels, and bone cell function and viability. Finally, we will summarize the recent studies regarding bone responses to mechanical unloading in Cx43 transgenic mouse models. The osteocyte has been perceived as the center of bone remodeling, and connexin channels enriched in osteocytes are a likely major player in meditating the function of bone. Based on numerous studies, connexin channels may present as a potential new therapeutic target in the treatment of bone loss and osteoporosis. This review will primarily focus on Cx43, with some discussion in other connexins expressed in bone cells. View Full-Text
Keywords: bone remodeling; mechanical loading; osteocytes; mechano-transduction; connexin43; hemichannels bone remodeling; mechanical loading; osteocytes; mechano-transduction; connexin43; hemichannels
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MDPI and ACS Style

Riquelme, M.A.; Cardenas, E.R.; Xu, H.; Jiang, J.X. The Role of Connexin Channels in the Response of Mechanical Loading and Unloading of Bone. Int. J. Mol. Sci. 2020, 21, 1146. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21031146

AMA Style

Riquelme MA, Cardenas ER, Xu H, Jiang JX. The Role of Connexin Channels in the Response of Mechanical Loading and Unloading of Bone. International Journal of Molecular Sciences. 2020; 21(3):1146. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21031146

Chicago/Turabian Style

Riquelme, Manuel A., Eduardo R. Cardenas, Huiyun Xu, and Jean X. Jiang 2020. "The Role of Connexin Channels in the Response of Mechanical Loading and Unloading of Bone" International Journal of Molecular Sciences 21, no. 3: 1146. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21031146

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