The emerging role of histone acetylation in rheumatic diseases: unraveling mechanisms and therapeutic prospects

Histone acetylation, a fundamental and reversible epigenetic modification, critically regulates chromatin structure and plays a pivotal role in diverse cellular processes, including gene transcription, cell cycle progression, and DNA damage repair. Rheumatic diseases [such as rheumatoid arthritis (RA), osteoarthritis (OA), and systemic lupus erythematosus (SLE)] represent a group of disorders primarily affecting joints, bones, muscles, and connective tissues, posing a significant global burden. This review systematically elucidated the aberrant regulation of histone acetylation in these rheumatic conditions, with a focus on the disrupted balance between histone acetyltransferases (HATs) and histone deacetylases (HDACs). We further discussed the downstream mechanisms driven by these acetylation alterations, which contribute to various pathological processes (including synovial inflammation, cartilage degradation, and dysregulated cell death). Notably, special emphasis is placed on the potential of traditional Chinese medicine (TCM) to target this epigenetic axis. We summarized evidence that TCM formulations can exert their therapeutic effects by modulating HAT/HDAC activity and restoring acetylation homeostasis. By integrating current knowledge, this review aimed to provide mechanistic insights and highlight the promising potential of targeting histone acetylation, especially through TCM-based strategies, for developing novel therapeutic strategies against rheumatic diseases.