Hypoxia enhances tenocyte differentiation of adipose-derived mesenchymal stem cells by inducing hypoxia-inducible factor-1α in a co-culture system

缺氧在共培养系统中诱导缺氧诱导因子-1α促进脂肪间充质干细胞向肌腱细胞分化

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Conclusions

Taken together, we found that growing ADMSCs under hypoxia, or activating expression of HIF-1α to be important in differentiation of ADMSCs, which provides a foundation for application of ADMSCs in vivo for tendon regeneration.

Methods

Human ADMSCs were co-cultured under normoxia (20% O2 ) and also under hypoxia (2% O2 ). Tenocyte differentiation of AMDSCs and expression of hypoxia-inducible factor-1 (HIF-1α) were analysed by reverse transcription-PCR, Western blotting and immunohistochemistry. Furthermore, HIF-1α inhibitor and inducer (FG-4592) effects on differentiation of AMDSCs were studied using qPCR, immunofluorescence and Western blotting.

Results

Indirect co-culture with tenocytes increased differentiation of ADMSCs into tenocytes; furthermore, hypoxia further enhanced tenocyte differentiation of AMDSCs, accompanied by increased expression of HIF-1α. HIF-1α inhibitor attenuated effects of hypoxia on differentiation of ADMSCs; in contrast, FG-4592 increased differentiation of ADMSCs under both hypoxia and normoxia. Conclusions: Taken together, we found that growing ADMSCs under hypoxia, or activating expression of HIF-1α to be important in differentiation of ADMSCs, which provides a foundation for application of ADMSCs in vivo for tendon regeneration.

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