title: Hypoxia enhances chondrogenesis and prevents terminal differentiation through PI3K/Akt/FoxO dependent anti-apoptotic effect.
abstract: 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.
authors.affiliation: 1] Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 100, Taiwan [2] Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan [3] Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Hsieh-Hsing
authors.initials: HH
authors.lastname: Lee
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Chang
authors.forename: Ming-Jium
authors.initials: MJ
authors.lastname: Shieh
authors.forename: Jung-Pan
authors.initials: JP
authors.lastname: Wang
authors.forename: Yi-Te
authors.initials: YT
authors.lastname: Chen
authors.forename: Tai-Horng
authors.initials: TH
authors.lastname: Young
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Hung
mesh_terms: D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002454:Cell Differentiation; D015687:Cell Hypoxia; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000502:physiology*; D004789:Enzyme Activation; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D051858:Forkhead Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053181:Caspase 8
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