A liver–cartilage selenium axis underlies metabolic comorbidity in osteoarthritis [Ribo-Seq]

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

In murine models of chronic and acute liver injury and metabolic dysfunction-associated steatotic hepatitis (MASH), hepatic dysfunction disrupts the SELENOP–ApoER2 axis, compromising selenium delivery to cartilage. Mechanistically, hepatic stress reduces hepatocyte SELENOP output through convergent transcriptional repression and translational suppression via ribosome collision on Sec-rich SELENOP transcripts. The resulting deficiency in cartilage selenoprotein synthesis promotes chondrocyte senescence, exacerbating OA.