Autor: |
Jong Min Lee, Ji-Yun Ko, Hye Young Kim, Jeong-Won Park, Farshid Guilak, Gun-Il Im |
Jazyk: |
angličtina |
Rok vydání: |
2019 |
Předmět: |
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Zdroj: |
Molecular Therapy: Nucleic Acids, Vol 17, Iss , Pp 310-322 (2019) |
Druh dokumentu: |
article |
ISSN: |
2162-2531 |
DOI: |
10.1016/j.omtn.2019.05.029 |
Popis: |
We investigated the functional role of miR-892b as a novel inhibitor of chondrocyte hypertrophy during TGF-β-mediated chondrogenesis of human mesenchymal stem cells (hMSCs). The expression of miR-892b during TGF-β-mediated chondrogenesis of hMSCs and the effects of miR-892b overexpression on chondrogenic and hypertrophic marker genes in the chondrogenesis of hMSCs were investigated. Targets of miR-892b were identified and verified by overexpression of synthetic miRNA mimics and luciferase assays. Cross-talk between Kruppel-like factor 10 (KLF10) and Indian hedgehog (Ihh) was investigated using KLF10 knockdown (KD). miR-892b enhanced chondrogenic makers and suppressed hypertrophy in hMSC chondrogenesis, mimicking parathyroid hormone-related peptide (PTHrP). KLF10, a transcription factor and miR-892b target, directly regulated Ihh promoter activity. Like miR-892b, KLF10 KD enhanced hMSC chondrogenesis and inhibited hypertrophy. Our findings suggest a key role of miR-892b in targeting the KLF10-Ihh axis as a regulator of hypertrophy in TGF-β-mediated chondrogenesis of hMSCs and provide a novel strategy for preventing hypertrophy in chondrogenesis from MSCs. Keywords: chondrogenesis, mesenchymal stem cells, hypertrophy, miR-892b, KLF10 |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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