Department of Orthopedic Surgery, Stanford University, Stanford, CA 94305, USA.
Department of Orthopedic Surgery, Stanford University, Stanford, CA 94305, USA.
Trends Pharmacol Sci. 2020 Aug;41(8):557-569. doi: 10.1016/j.tips.2020.05.008. Epub 2020 Jun 22.
Osteoarthritis (OA) is an age-associated disease characterized by chronic joint pain resulting from degradation of articular cartilage, inflammation of the synovial lining, and changes to the subchondral bone. Despite the wide prevalence, no FDA-approved disease-modifying drugs exist. Recent evidence has demonstrated that epigenetic dysregulation of multiple molecular pathways underlies OA pathogenesis, providing a new mechanistic and therapeutic axis with the advantage of targeting multiple deregulated pathways simultaneously. In this review, we focus on the epigenetic regulators that have been implicated in OA, their individual roles, and potential crosstalk. Finally, we discuss the pharmacological molecules that can modulate their activities and discuss the potential advantages and challenges associated with epigenome-based therapeutics for OA.
骨关节炎（OA）是一种与年龄相关的疾病，其特征为慢性关节疼痛，源于关节软骨降解、滑膜衬里炎症和软骨下骨改变。尽管其广泛流行，但目前尚无美国食品和药物管理局批准的疾病修正药物。最近的证据表明，多个分子途径的表观遗传失调是 OA 发病机制的基础，为同时靶向多个失调途径提供了新的机制和治疗轴。在这篇综述中，我们重点讨论了与 OA 相关的表观遗传调节剂、它们的单独作用以及潜在的串扰。最后，我们讨论了可以调节它们活性的药理学分子，并讨论了基于表观基因组的 OA 治疗相关的潜在优势和挑战。
