Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by the slow degeneration of joint components that primarily affects the elderly. There is currently no cure for OA; thus, treatment focuses on symptom reduction. This article investigates the potential of talarozole, a retinoic acid metabolism-blocking agent (RAMBA), as a new treatment for hand OA. Talarozole showed promising results by inhibiting retinoic acid degradation and increasing its levels in the body. Six hours after destabilization of the medial meniscus, talarozole significantly reduced inflammation in mice's cartilage. The findings underscore the importance of the protein encoded by the ALDH1A2 gene in retinoic acid metabolism, shedding light on its potential implications for the management of OA. Maintaining adequate retinoic acid levels may help to reduce mechano-inflammatory gene regulation. Furthermore, RAMBAs like talarozole may emerge as disease-modifying OA therapies, promising improved symptom control and slower disease progression. In conclusion, this research provides critical genetic insights into severe hand OA and promotes talarozole as a prospective therapy option. These findings pave the door for additional research that could revolutionize OA treatment by targeting retinoic acid metabolism to reduce symptoms and slow disease progression.