112年1月12日（四）12：30於3樓和氣會議室舉辦「研究發想會」，由高雄長庚紀念醫院醫研部動物型態鑑定暨診斷核心實驗室連韋雄博士主講「表觀基因調控於關節軟骨、腸道菌相及骨關節炎病理機轉研究」，歡迎有興趣的同仁前往聆聽。

本次講座摘要：

Knee joint osteoarthritis (OA) is the most prevalent musculoskeletal disease. Multiple risk factors affect the increased rate of arthritis, such as age, genetics, gender, and lifestyle. Epigenomics has emerged as a critical player in our rapidly growing evidence for understanding OA. Epigenetic modification describes three significant phenomena in the regulation of OA pathogenesis, histone modification, DNA methylation, and non-coding RNA. However, the epigenome-wide examination of degenerative disease in detailed approaches of this kind carries various well-known limitations. We successfully generated cartilage-specific UTX-KO mice (Col2-Cre-UTX-loxp/loxp), and maintenance of articular cartilage integrity prevented destabilization of the medial meniscus-induced degenerative articular cartilage injury. The ChIP-seq analysis revealed enrichment of H3K27me3 at UTX deficiency primary chondrocytes. We are signaling UTX, PRC2 containing EZH2 in dynamics managing gene expression through H3K27 methylation, which significantly affects chromatin remodeling on embryo development, disease progression, and tissue regeneration.

Furthermore, epigenetic reprogramming drives the impact of metabolite composition and various microorganisms in degenerative disease. The host’s genetic background influences gut microbiome diversity through mucosa permeability, gut structure, and metabolites. Previous studies have shown that intestinal microbiota dysbiosis in the elder is relevant to the development of OA. Preliminary analysis revealed that aged mice deficient in UTX showed mild OA signs, like moderate cartilage injury and osteophyte formation, compared to severe OA of aged wild-type mice. Gut microbiota alteration for increased probiotics Lactobacilli and metabolomics, like fatty acid metabolism, existed in UTX-KO mice. In vitro, UTX deletion and microbiota-derived short-chain fatty acid butyrate treatment improved chondrocyte markers expression and extracellular matrix synthesis in inflamed chondrocytes.
In conclusion, this study conveys evidence on genetic background and epigenomic regulation. It reveals gut microbiota metabolites and hosts in reciprocal mechanisms that modulate the cartilage degeneration process in knee OA.