Melatonin abolished proinflammatory factor expression and antagonized osteoarthritis progression in vivo

Autor: Shan-Chi Liu, Chun-Hao Tsai, Yu-Han Wang, Chen-Ming Su, Hsi-Chin Wu, Yi-Chin Fong, Shun-Fa Yang, Chih-Hsin Tang
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cell Death and Disease, Vol 13, Iss 3, Pp 1-10 (2022)
Druh dokumentu: article
ISSN: 2041-4889
DOI: 10.1038/s41419-022-04656-5
Popis: Abstract Progressive structural changes in osteoarthritis (OA) involve synovial inflammation and angiogenesis, as well as activation of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL)-8, and the angiogenic factor vascular endothelial growth factor (VEGF). The endogenous hormone melatonin (N-acetyl-5-methoxytryptamine) is involved in antioxidative and anti-inflammatory activities, but how it antagonizes OA progression via its specific receptors is unclear. Here, we demonstrate that the MT1 melatonin receptor, but not the MT2 receptor, is highly expressed in normal tissue and only minimally in OA tissue. By targeting the MT1 receptor, melatonin reversed OA-induced pathology and effectively reduced levels of TNF-α, IL-8, and VEGF expression in OA synovial fibroblasts and synovium from rats with severe OA. Interestingly, we found that the anabolic activities of melatonin involved the MT1 receptor, which upregulated microRNA-185a through the PI3K/Akt and ERK signaling pathways in OA synovial fibroblasts. Our investigation confirms the role of the MT1 receptor in melatonin-induced anti-catabolic effects in OA disease.
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