期刊
AGING-US
卷 11, 期 12, 页码 4075-4089出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.102038
关键词
osteoarthritis; TGF-beta 1; FOXO3; miRNA-92a; synovial fibroblasts
资金
- Taiwan's Ministry of Science and Technology [MOST 105-2320-B-039-015-MY3, 107-2314-B-039-064-, 107-2314-B-039-014-, 107-2320-B-039-019-MY3]
- China Medical University [CMU 107-ASIA-09]
Osteoarthritis (OA) is an age-related disease marked by synovial inflammation and cartilage destruction arising from synovitis, joint swelling and pain. OA therapy that targets the synovium is a promising strategy for mitigating the symptoms and disease progression. Altered activity of the transforming growth factor-beta 1 isoform (TGF-beta 1) during aging underlies OA progression. Notably, aberrant forkhead box class O 3 (FOXO3) activity is implicated in the pathogenesis of various age-related diseases, including OA. This study explored the interaction and cross-talk of TGF-beta 1 and FOXO3 in human osteoarthritis synovial fibroblasts (OASFs). TGF-beta 1 stimulated FOXO3 synthesis in OASFs, which was mitigated by blocking adenosine monophosphate-activated protein kinase (AMPK) and p38 activity. TGF-beta 1 also inhibited the expression of miR-92a, which suppresses FOXO3 transcription. The suppression of miR-92a was effectively reversed with the blockade of the AMPK and p38 pathways. Our study showed that TGF-beta 1 promotes anti-inflammatory FOXO3 expression by stimulating the phosphorylation of AMPK and p38 and suppressing the downstream expression of miR-92a. These results may help to clarify OA pathogenesis and lead to better targeted treatment.
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