A liver–cartilage selenium axis underlies metabolic comorbidity in osteoarthritis [RNA-seq]

Here, we identify a liver–cartilage micronutrient axis, in which hepatic dysfunction promotes OA progression through impaired selenium metabolism. Analysis of nationwide epidemiological cohorts reveal elevated OA prevalence among individuals with liver disease.

Mechanistic studies using murine models of chronic and acute liver injury, as well as metabolic dysfunction-associated steatotic hepatitis (MASH), demonstrate that hepatic dysfunction disrupts the SELENOP–ApoER2 axis, compromising selenium delivery to cartilage. The resulting deficiency in selenoprotein synthesis promotes chondrocyte senescence, ultimately exacerbating OA pathogenesis. Notably, inorganic selenium supplementation restores selenoprotein expression and alleviates OA severity despite persistent liver pathology, highlighting selenium as a nutritionally modifiable factor in this inter-organ comorbidity.