Gap junctional communication in bone: Role in cell function and disease

PURPOSE OF REVIEW: This review examines the expanding role of gap junction proteins, connexins, in the function of osteoblastic cells and the consequences of disrupted connexin function in the pathology of human disease. RECENT FINDINGS: Recent data have revealed a critical function for gap junction proteins in regulating cellular responses to extracellular cues, including growth factor stimulation and mechanical load. Further, molecular details as to how alterations in connexin function can alter cell-cell signalling have begun to emerge. In addition, recent work has revealed that mutations in connexins can lead to the human disease, oculodentodigital dysplasia. A mouse model presenting with an oculodentodigital dysplasia-like phenotype has begun to shed light on how gap junctions may affect skeletal function. Moreover, the recent identification of connexin40 in skeletal patterning associated with Holt-Oram syndrome has advanced the notion that gap junction proteins are important regulators of skeletal development. SUMMARY: By expanding our knowledge of gap junction function and regulation, as well as our understanding of the role of connexins in development and disease, we can begin to shape strategies to target connexins in order to regulate bone mass, hormonal and mechano-responsiveness and perhaps treat human conditions such as oculodentodigital dysplasia and Holt-Oram syndrome.