Hypoxia Enhances Chondrogenesis and Prevents Terminal Differentiation through PI3K/Akt/FoxO Dependent Anti-Apoptotic Effect

被引：0

作者：

Hsieh-Hsing Lee

Chia-Chi Chang

Ming-Jium Shieh

Jung-Pan Wang

Yi-Te Chen

Tai-Horng Young

Shih-Chieh Hung

机构：

[1] National Taiwan University,Institute of Biomedical Engineering, College of Medicine and College of Engineering

[2] Shuang Ho Hospital,Department of Orthopedics

[3] Taipei Medical University,Department of Orthopedics

[4] School of Medicine,Department of Medical Research and Education

[5] College of Medicine,Department of Orthopaedics and Traumatology

[6] Taipei Medical University,Department of Orthopedics and Traumatology

[7] Institute of Clinical Medicine,undefined

[8] Institute of Pharmacology,undefined

[9] National Yang-Ming University,undefined

[10] Stem Cell Laboratory,undefined

[11] Taipei Veterans General Hospital,undefined

[12] Shin Kong Wu Ho-Su Memorial Hospital,undefined

[13] School of Medicine,undefined

[14] Fu-Jen Catholic University,undefined

来源：

Scientific Reports | / 3卷

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摘要：

Hypoxia, a common environmental condition, influences cell signals and functions. Here, we compared the effects of hypoxia (1% oxygen) and normoxia (air) on chondrogenic differentiation of human mesenchymal stem cells (MSCs). For in vitro chondrogenic differentiation, MSCs were concentrated to form pellets and subjected to conditions appropriate for chondrogenic differentiation under normoxia and hypoxia, followed by the analysis for the expression of genes and proteins of chondrogenesis and endochondral ossification. MSCs induced for differentiation under hypoxia increased in chondrogenesis, but decreased in endochondral ossification compared to those under normoxia. MSCs induced for differentiation were more resistant to apoptosis under hypoxia compared to those under normoxia. The hypoxia-dependent protection of MSCs from chondrogenesis-induced apoptosis correlated with an increase in the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/FoxO pathway. These results suggest that the PI3K/Akt/FoxO survival pathway activated by hypoxia in MSCs enhances chondrogenesis and plays an important role in preventing endochondral ossification.

引用

共 111 条

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