ArticleGerontology2024
Targeting Cartilage miR-195/497 Cluster for Osteoarthritis Treatment Regulates the Circadian Clock.
Article in Gerontology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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7 authors at 1 institution in 1 country.
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Abstract
introductionOsteoarthritis (OA) is the most prevalent and debilitating joint disease without an effective therapeutic option. Multiple risk factors for OA have been identified, including abnormal chondrocyte miRNA secretion and circadian rhythms disruption, both of which have been found to cause progressive damage and loss of articular cartilage. Environmental disruption of circadian rhythms in mice predisposes animals to cartilage injury and OA.
methodsThe role of miR-195/497 cluster during OA progression was verified by mouse OA model with intra-articular injection of Agomir and Antagomir. We performed micro-CT analysis, Osteoarthritis Research Society International scores, and histological analysis in mouse knee joints. RNA sequencing was performed on the mouse cartilage cell line to explore the molecular mechanism of the miR-195/497 cluster and proteins in signaling pathway were evaluated using Western blot. Senescence-associated phenotypes were detected by Western blot, senescence β-galactosidase staining, and immunofluorescence.
resultsThis study demonstrated that miR-195/497-5p expression is disrupted in OA with senescent chondrocytes. In addition, miR-195/497-5p influenced the circadian rhythm of mice chondrocytes by modulating the expression of the Per2 protein, resulting in the gradual degradation of articular cartilage. We found that the miR-195/497 cluster targets DUSP3 expression. The deletion of the miR-195/497 cluster increased the level of DUSP3 expression and decreased the levels of phosphorylated ERK 1/2 and CREB. Per2 transcription is upregulated by stimulating CREB and ERK 1/2 phosphorylation.
conclusionOur findings identify a regulatory mechanism connecting chondrocyte miR-195/497-5p to cartilage maintenance and repair and imply that circadian rhythm disturbances affected by miR-195/497-5p are risk factors for age-related joint diseases such as OA.
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