ALKBH5 facilitates CYP1B1 mRNA degradation via m6A demethylation to alleviate MSC senescence and osteoarthritis progression

Experimental & Molecular Medicine, Published online: 01 August 2023; doi:10.1038/s12276-023-01059-0The age-related modification of adult stem cells, known as mesenchymal stem cells (MSCs), could be targeted to alleviate the progression of osteoarthritis. The deterioration of cellular functions due to aging (or ‘senescence’) of MSCs is linked to the development of diseases including osteoarthritis. A common RNA modification in mammal cells, m6A, plays vital roles in cellular functioning. Guiwen Ye at Sun Yat-sen University in Shenzhen, China, and co-workers used patient cell lines and mouse models to show that m6A levels are enhanced in aging MSCs. This increase is due to reduced expression of a key protein called ALKBH5 and modifies the behavior of a molecule found in MSC mitochondria called CYP1B1. This leads to mitochondrial dysfunction and MSC senescence. Knocking out the Alkbh5 gene in mouse MSCs aggravated osteoarthritis, while boosting Alkbh5 expression in MSCs reduced osteoarthritis progression.
Source: Experimental and Molecular Medicine - Category: Molecular Biology Authors: Source Type: research