Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 36, Issue 5, Pages 1753-1766Publisher
KARGER
DOI: 10.1159/000430148
Keywords
Osteoarthritis; Chondrogenesis; Cartilage degeneration; MiR-381; Metalloproteinase-13
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Funding
- Guangzhou Elite Project [SuiJing [2014] 7, JY201420]
- National Natural Science Foundation of China [81301558, 81171709, 81201388, 81371941]
- Doctoral Scientific Fund Project of the Ministry of Education of China [20130171120074]
- Basic scientific training project for young medical teachers of Sun Yat-sen University [15ykpy11]
- Natural Science Foundation of Guangdong Province, China [2013040016269]
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Aim: The molecular pathways regulating cartilage degradation are unclear. miR-381 was identified as a putative regulator of chondrogenesis related genes. Here, we examined its role in chondrogenesis and osteoarthritic cartilage degeneration. Methods: miR-381 expression was assessed in vitro in response to IL-1 beta stimulation in primary human (PHC) and mouse (PMC) chondrocytes, and ATDC5 derived chondrocytes; and in vivo in mouse embryos and human osteoarthritic cartilage. The effects of miR-381 on chondrogenesis and NF-kB signaling were assessed using a synthetic RNA mimic or inhibitor and luciferase assay, respectively. Upstream regulators of miR381 were probed using siRNA or overexpression plasmids for Sox9 and Runx2. Results: miR-381 expression was elevated in chondrogenic and hypertrophic ATDC5 cells. miR-381 was induced in vitro by IL-1 beta in ATDC5 cells, PMCs, and PHCs, and was expressed in areas of cartilage degradation or absorption in vivo. Overexpression of Runx2 or Sox9 increased miR-381 expression in ATDC5 cells. miR-381 suppressed expression of collagen, type II, alpha 1, and enhanced expression of metalloproteinase-13 (MMP-13), but did not regulate NFKBIA and NKRF activity. Conclusion: miR-381 was highly expressed during chondrogenesis and in arthritic cartilage. It may contribute to absorption of the cartilage matrix by repressing type II collagen and inducing MMP-13. Copyright (C) 2015 S. Karger AG, Basel
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