-mediated caffeine metabolism involves ferroptosis of osteoblasts in osteoarthritis.

Abstract

There is a positive causality between coffee consumption and osteoarthritis (OA); however, whether gut microbiota is involved needs to be discussed. Here, we observed that in caffeine consumers, fecalabundance was positively correlated with subchondral bone mass, serum caffeine concentration was negatively correlated with bone mass, and fecalwas negatively correlated with serum caffeine. In the OA model, caffeine intake aggravated articular cartilage destruction, bone mass loss, and intestinal barrier damage; on the contrary, paraxanthine intake reversed the above lesions. Importantly, after the intestinalsupplement, caffeine-induced lesions in OA mice were effectively alleviated. Mechanically,has the potential to metabolize caffeine into paraxanthine, and this effect could alleviate the ferroptosis of osteoblast in the OA model. This study screened out thatan endogenous bacteria, has the ability to metabolize caffeine and revealed its effects on OA progression.IMPORTANCEThere is positive causality between coffee consumption and osteoarthritis (OA). Caffeine exposure is responsible for the reduction of bone mass and restrained osteoblast function.abundance is exhausted in gut and positively correlated with subchondral bone mass in coffee consumption patients with OA. Supplement of intestinalalleviates caffeine-induced subchondral bone loss.has the potential to metabolize caffeine into paraxanthine, and this effect alleviates ferroptosis of osteoblast. Our study illustrated that intestinalpossibly serves as a novel promising treatment for coffee consumers with OA.