Research Paper Volume 11, Issue 12 pp 4075—4089
TGF-β1 enhances FOXO3 expression in human synovial fibroblasts by inhibiting miR-92a through AMPK and p38 pathways
- 1 School of Medicine, China Medical University, Taichung, Taiwan
- 2 Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
- 3 Department of Medical Education and Research, China Medical University Beigang Hospital, Yunlin, Taiwan
- 4 Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
- 5 Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
- 6 Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
received: January 28, 2019 ; accepted: June 14, 2019 ; published: June 21, 2019 ;https://doi.org/10.18632/aging.102038
How to Cite
Copyright: Kuo et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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-β1 isoform (TGF-β1) 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-β1 and FOXO3 in human osteoarthritis synovial fibroblasts (OASFs). TGF-β1 stimulated FOXO3 synthesis in OASFs, which was mitigated by blocking adenosine monophosphate-activated protein kinase (AMPK) and p38 activity. TGF-β1 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-β1 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.