Chondrogenesis occurs in vivo in a hypoxic environment, in which the hypoxia inducible factor 1, HIF-1, plays a regulatory role, possibly mediated through the transcription factor DEC1. We have analyzed the effect of hypoxia (1% oxygen) alone and in combination with insulin on the chondrogenic differentiation of the mouse embryonic stem cell line ATDC5. Hypoxic treatment alone induced early chondrogenesis as evidenced by enhanced expression of aggrecan and collagen II, whereas hypoxic incubation of insulin-treated cells delayed and suppressed insulin-mediated early chondrogenesis and almost completely blocked hypertrophic differentiation. Paradoxically, the transcriptional activation of DEC1 was invariably enhanced by the hypoxic exposure.

译文

软骨发生在体内低氧环境中,其中低氧诱导因子1 HIF-1发挥调节作用,可能通过转录因子dec1介导。我们已经分析了单独缺氧 (1% 氧) 以及与胰岛素联合使用对小鼠胚胎干细胞系atdc5软骨分化的影响。单独的低氧治疗可诱导早期软骨形成,这可以通过增强聚集蛋白聚糖和胶原蛋白II的表达来证明,而胰岛素处理的细胞的低氧孵育会延迟并抑制胰岛素介导的早期软骨形成,并且几乎完全阻断了肥厚分化。矛盾的是,低氧暴露总是会增强DEC1的转录激活。

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