Targeting epigenetic modifiers in osteoarthritis: from biological insights to pre-clinical practice

Osteoarthritis (OA), characterized by the whole joint degeneration, is one of the most common joint diseases worldwide, and more than 37% people at 60 years of age or older will develop OA. So far, the exact mechanism of OA pathogenesis remains unclear, and the search for an effective disease-modifying approach for OA has been unsuccessful. Epigenetic alterations refer to heritable changes in chromatin organization and biochemical composition that do not involve changes to the DNA sequence itself. Recently, the roles of epigenetic modifications in ageing-related diseases have been widely studied, and numerous OA-involved epigenetic targets have been identified. The disruption of epigenetic information is regarded as a reversible cause of OA. In this review, the most recent studies on pathological processes and epigenetic changes relevant to OA, encompassing different subtypes (knee/hip/spinal, and temporomandibular joint-OA), various epigenetic modulations (DNA methylation, histone modification, non-coding RNAs, and RNA methylation), and therapeutic signaling pathways have been integrated. The current therapies targeting epigenetic machinery, future directions for epigenetic illustrations in OA, and potential epigenetic interventions and epigenetic disease modifying-OA drugs are also further described.