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Semin Cell Dev Biol. 2016 Feb;50:31-9. doi: 10.1016/j.semcdb.2015.12.017. Epub 2015 Dec 29.

Connexins in the skeleton.

Author information

1
Department of Orthopaedics, University of Maryland, School of Medicine, Baltimore, MD, United States.
2
Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University in St. Louis, Campus Box 8301, 425 South Euclid, St. Louis, MO 63110, United States. Electronic address: rcivitel@dom.wustl.edu.

Abstract

Shaping of the skeleton (modeling) and its maintenance throughout life (remodeling) require coordinated activity among bone forming (osteoblasts) and resorbing cells (osteoclasts) and osteocytes (bone embedded cells). The gap junction protein connexin43 (Cx43) has emerged as a key modulator of skeletal growth and homeostasis. The skeletal developmental abnormalities present in oculodentodigital and craniometaphyseal dysplasias, both linked to Cx43 gene (GJA1) mutations, demonstrate that the skeleton is a major site of Cx43 action. Via direct action on osteolineage cells, including altering production of pro-osteoclastogenic factors, Cx43 contributes to peak bone mass acquisition, cortical modeling of long bones, and maintenance of bone quality. Cx43 also contributes in diverse ways to bone responsiveness to hormonal and mechanical signals. Skeletal biology research has revealed the complexity of Cx43 function; in addition to forming gap junctions and "hemichannels", Cx43 provides a scaffold for signaling molecules. Hence, Cx43 actively participates in generation and modulation of cellular signals driving skeletal development and homeostasis. Pharmacological interference with Cx43 may in the future help remedy deterioration of bone quality occurring with aging, disuse and hormonal imbalances.

KEYWORDS:

Bone; Cx37; Cx43; Gap junction; Signal transduction

PMID:
26740471
PMCID:
PMC4779380
DOI:
10.1016/j.semcdb.2015.12.017
[Indexed for MEDLINE]
Free PMC Article

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