Therapeutic senescence via GPCR activation in synovial fibroblasts facilitates resolution of arthritis.

ABSTRACT: Rheumatoid arthritis affects individuals commonly during the most productive years of adulthood. Poor response rates and high costs associated with treatment mandate the search for new therapies. Here we show that targeting a specific G-protein coupled receptor promotes senescence in synovial fibroblasts, enabling amelioration of joint inflammation. Following activation of the melanocortin type 1 receptor (MC₁), synovial fibroblasts acquire a senescence phenotype characterized by arrested proliferation, metabolic re-programming and marked gene alteration resembling the remodeling phase of wound healing, with increased matrix metalloproteinase expression and reduced collagen production. This biological response is attained by selective agonism of MC₁, not shared by non

SUBMITTER: Montero-Melendez T 

PROVIDER: S-EPMC7005314 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature