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首页> 外文期刊>Journal of cellular biochemistry. >Endothelin-1 inhibits human osteoblastic cell differentiation: influence of connexin-43 expression level.
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Endothelin-1 inhibits human osteoblastic cell differentiation: influence of connexin-43 expression level.

机译：内皮素1抑制人成骨细胞分化：连接蛋白43表达水平的影响。

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摘要

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.
机译：间隙连接细胞间通讯（GJIC）允许在发育和分化过程中协调的细胞活动。在骨骼中，以前已经证明了间隙连接蛋白，连接蛋白43（Cx43）和GJIC参与成骨细胞分化和细胞外基质矿化。以前的研究表明，内皮素-1（ET-1）也与成骨细胞增殖和分化的控制有关。但是，根据细胞模型，已显示ET-1会减少或增加成骨细胞分化标记。由于尚无关于ET-1对成骨细胞中GJIC和Cx43表达的影响的数据，因此在此我们分析了人类细胞系（hFOB 1.19）中Cx43与ET-1之间可能的串扰，当人为时，Cx43和ET-1显示不同的Cx43表达水平和表型培养在33.5或39摄氏度下进行。培养2-12天的ET-1（10（-8）M）的存在并不显着改变hFOB细胞的增殖率，无论其表型如何。相反，ET-1对生化分化标记物（碱性磷酸酶活性和骨钙素表达）具有不同的抑制作用，在39摄氏度时显着降低了分化表型，而在33.5摄氏度时未观察到任何作用。在转录水平和蛋白水平上均与GJIC和Cx43的降低有关。总之，我们的结果表明Cx43表达水平可能影响ET-1对人成骨细胞分化的作用。我们的数据还表明，间隙连接蛋白可能在成骨细胞对涉及骨病理学的促有丝分裂因子的反应中起关键作用。

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