RNA-seq analysis of hand osteoarthritis cartilage reveals a reciprocal regulation between retinoic acid and markers of cell senescence, identifying talarozole as a novel targeting strategy in hand osteoarthritis

Abstract

Purpose: Hand is the most prevalent site affected by OA. Hypomorphic variants in ALDH1A2, the gene that encodes the key enzyme in the synthesis of all-trans retinoic acid (atRA), have been associated with severe hand OA. atRA appears to be key in the articular cartilage injury response; dropping rapidly upon cartilage injury and being able to suppress mechanically induced inflammatory genes (OARSI abstract 2018). In this study, we performed an RNA-seq analysis to identify pathways regulated in hand OA that are influenced by endogenous (genetically determined) levels of atRA, by stratifying patient samples into those that did or did not carry the ALDH1A2 polymorphic variants.