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Article Dans Une Revue Journal of Cellular Biochemistry Année : 2008

Endothelin-1 inhibits human osteoblastic cell differentiation: influence of connexin-43 expression level.

Résumé

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 degrees 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 degrees C, whereas no effects were measured at 33.5 degrees 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.

Dates et versions

hal-00431039 , version 1 (10-11-2009)

Identifiants

Citer

Corinne Niger, Graziello Greneau, Céline Fiorini, Norah Defamie, Georges Pointis, et al.. Endothelin-1 inhibits human osteoblastic cell differentiation: influence of connexin-43 expression level.. Journal of Cellular Biochemistry, 2008, 103, pp.110-122. ⟨10.1002/jcb.21390⟩. ⟨hal-00431039⟩
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