Gap junction and hemichannel functions in osteocytes

Cell-to-cell and cell-to-matrix communication in bone cells mediated by gap junctions and hemichannels, respectively, maintains bone homeostasis. Gap junctional communication between cells permits the passage of small molecules including calcium and cyclic AMP. This cell-to-cell communication occurs between bone cells including osteoblasts, osteoclasts and osteocytes, and is important in both bone formation and bone resorption. Connexin (Cx) 43 is the predominant gap junction protein in bone cells, and facilitates the communication of cellular signals either through docking of gap junctions between two cells, or through the formation of un-paired hemichannels. Systemic deletion of Cx43 results in perinatal lethality, so conditional deletion models are necessary to study the postnatal role of gap junctions in bone. These models provide the opportunity to determine the role of gap junctions in specific bone cells, notably the osteocyte. In this review, we summarize the key roles that gap junctions and hemichannels in osteocytes play in bone cell response to many stimuli including mechanical loading, intracellular and extracellular stimuli, such as parathyroid hormone, PGE2, plasma calcium levels and pH, as well as in maintaining osteocyte survival.This article is part of a Special Issue entitled "The Osteocyte".

► Cherubism is a rare and disfiguring genetic disorder with excessive bone resorption and multilocular lesions in the mandible and/or maxilla.
► Findings in the cherubism mouse model suggest that removal of TNF-α prevents development of the bone phenotype.
► We treated two children with active cherubism with the TNF-α antagonist adalimumab for approximately 2.5 years.
► The treatment appeared to decrease the formation of giant cells, but did not induce lesion regression or prevent lesion expansion.
► TNF-α antagonist treatment does not appear to provide sufficient amelioration for patients suffering from cherubism.