Abstract
Gap junctional intercellular communication (GJIC) permits coordinated cellular activities during developmental and differentiation processes. In bone, the involvement of the gap junctional protein, connexin‐43 (Cx43), and of GJIC in osteoblastic differentiation and mineralization of the extracellular matrix has been previously demonstrated. Former studies have shown that endothelin‐1 (ET‐1) was also implicated in the control of osteoblastic proliferation and differentiation. However, depending on the cellular models, ET‐1 has been shown to decrease or increase osteoblastic differentiation markers. As no data were available on the ET‐1 effect on GJIC and Cx43 expression in osteoblastic cells, we analyzed here the possible crosstalk between Cx43 and ET‐1 in a human cell line (hFOB 1.19) which displays different Cx43 expression levels and phenotypes when cultured at 33.5 or 39°C. The presence of ET‐1 (10^−8^ M) for 2–12 days of culture did not significantly alter the proliferation rate of hFOB cells whatever their phenotype. In contrast, ET‐1 induced a differential inhibitory effect on the biochemical differentiation markers (alkaline phosphatase activity and osteocalcin expression) with a significant reduction in the differentiated phenotype at 39°C, whereas no effects were measured at 33.5°C. The inhibitory effect was linked to a decrease of GJIC and of Cx43 both at transcriptional and protein levels. Altogether, our results suggest that Cx43 expression level could influence the action of ET‐1 on human osteoblastic cell differentiation. Our data also indicate that the gap junctional protein could play a pivotal role in the response of osteoblasts to mitogenic factors implicated in bone pathologies. J. Cell. Biochem. 103: 110–122, 2008. © 2007 Wiley‐Liss, Inc.