In:
Cell Death & Disease, Springer Science and Business Media LLC, Vol. 13, No. 3 ( 2022-03-07)
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 MT 1 melatonin receptor, but not the MT 2 receptor, is highly expressed in normal tissue and only minimally in OA tissue. By targeting the MT 1 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 MT 1 receptor, which upregulated microRNA-185a through the PI3K/Akt and ERK signaling pathways in OA synovial fibroblasts. Our investigation confirms the role of the MT 1 receptor in melatonin-induced anti-catabolic effects in OA disease.
Type of Medium:
Online Resource
ISSN:
2041-4889
DOI:
10.1038/s41419-022-04656-5
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2541626-1
Permalink
