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Connexins in Skeletal Biology

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Connexins

Abstract

The skeleton is a dynamic structure that constantly remodels in response to local and systemic stimuli to meet the needs of structural integrity, mechanical competence, and maintenance of mineral homeostasis. Control of bone remodeling requires coordinated activity among osteoblasts, osteocytes, and osteoclasts. In recent years, knowledge about the biological role of connexins in the skeletal system has significantly advanced, primarily as a result of studies involving mouse and human connexin genetics. Cx43, the most abundant gap junction protein in the skeleton, is required for normal skeletal development (bone modeling) and for its maintenance in postnatal life (bone remodeling). These biological functions are underscored by the skeletal malformations and severe osteopenia present in oculodentodigital dysplasia, a disease linked to CX43 gene (GJA1) mutations, and by Gja1 ablation in mice. Cx43 modulates osteoblast differentiation and function by allowing full responses to extracellular cues via upregulation of specific signaling pathways converging on connexin-sensitive transcriptional units. Other connexins are present in the skeletal tissue, but their function is only partially understood. Gap junctional intercellular communication and gap junction hemichannels are also critical in mechanostransduction, functioning to integrate and amplify mechanical signals throughout bone cell networks.

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Acknowledgments

This work was supported by National Institutes of Health (NIH) grants AR41255 (to RC) and AG13087-11 (to HD). We also thank Amanda Taylor, Ryan Riddle, and Jung Lim for help in preparing the manuscript.

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  1. Department of Internal Medicine, Division of Bone and Mineral Diseases, 660 South Euclid Avenue, PO Box 8301, St. Louis, MO 63110, US

    Roberto Civitelli

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Correspondence to Roberto Civitelli .

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  1. New Jersey Medical School UMDNJ, Newark, NJ, USA

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Civitelli, R., Donahue, H.J. (2009). Connexins in Skeletal Biology. In: Harris, A.L., Locke, D. (eds) Connexins. Humana Press. https://doi.org/10.1007/978-1-59745-489-6_17

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