Response splicing quantitative trait loci in primary human chondrocytes identify putative osteoarthritis risk genes.

ABSTRACT: Osteoarthritis affects millions worldwide, yet effective treatments remain elusive due to poorly understood molecular mechanisms. While genome-wide association studies (GWAS) have identified hundreds of osteoarthritis-associated loci, identifying the genes impacted at each locus remains challenging. We investigate alternative splicing using RNA-sequencing data from 101 human chondrocyte samples treated with phosphate-buffered saline or fibronectin fragment, an osteoarthritis trigger. We identified 590 differentially spliced genes between conditions, with FN-f inducing splicing events similar to those in primary osteoarthritis tissue. CRISPR/Cas9 mimicking of an SNRNP70 splicing event observed in osteoarthritis induced an osteoarthritis-like expression pattern. Integration with genotyping d

SUBMITTER: Byun S 

PROVIDER: S-EPMC12381304 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature