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

ABSTRACT: While osteoarthritis (OA) has traditionally been viewed as a localized joint disorder, systemic metabolic dysfunction is increasingly recognized as a key contributor to its pathogenesis. 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. Inorganic selenium supplementation restores cartilage selenoprotein expression and alleviates OA despite persistent liver pathology, highlighting selenium as a nutritionally modifiable factor. Our findings open preventive strategies against joint comorbidity in the growing population with metabolic liver disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE334076 | GEO | 2026/09/12

REPOSITORIES: GEO

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

Project description:While osteoarthritis (OA) has traditionally been viewed as a localized joint disorder, systemic metabolic dysfunction is increasingly recognized as a key contributor to its pathogenesis. 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. Collectively, our findings suggest new opportunities for preventive strategies to reduce joint comorbidity in the growing population with metabolic liver disease.

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