Huang Jingyi, Liu Ming, Furey Andrew, Rahman Proton, Zhai Guangju
Human Genetics & Genomics, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, St. John's, Newfoundland & Labrador, A1B 3V6, Canada.
Discipline of Orthopaedic Surgery, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, St. John's, Newfoundland & Labrador, Canada A1B 3V6 & Office of the Premier, Government of Newfoundland & Labrador, 100 Prince Philip Drive, St. John's, Newfoundland & Labrador, A1B 4J6, Canada.
Hum Mol Genet. 2025 Feb 17;34(5):444-453. doi: 10.1093/hmg/ddae200.
Cartilage degradation is the hallmark of osteoarthritis (OA). The purpose of this study was to identify and validate differentially expressed genes (DEGs) in human articular cartilage that could serve as potential therapeutic targets for hip OA. We performed transcriptomic profiling in a discovery cohort (12 OA-free and 72 hip OA-affected cartilage) and identified 179 DEGs between OA-free and OA-affected cartilage after correcting for multiple testing (P < 2.97 × 10-6). Pathway and network analyses found eight hub genes to be associated with hip OA (ASPN, COL1A2, MXRA5, P3H1, PCOLCE, SDC1, SPARC, and TLR2), which were all confirmed using qPCR in a validation cohort (36 OA-free and 62 hip OA-affected cartilage) (P < 6.25 × 10-3). Our data showed that dysregulation of extracellular matrix formation and imbalance in the proportion of collagen chains may contribute to the development of hip OA, and SDC1 could be a promising potential therapeutic target. These findings provided a better understanding of the molecular mechanisms for hip OA and may assist in developing targeted treatment strategies.
软骨降解是骨关节炎（OA）的标志。本研究的目的是鉴定和验证人类关节软骨中差异表达基因（DEG），这些基因可作为髋骨关节炎的潜在治疗靶点。我们在一个发现队列（12个无OA和72个受髋OA影响的软骨）中进行了转录组分析，并在多重检验校正后，确定了无OA和受OA影响的软骨之间的179个DEG（P < 2.97×10-6）。通路和网络分析发现8个枢纽基因与髋OA相关（ASPN、COL1A2、MXRA5、P3H1、PCOLCE、SDC1、SPARC和TLR2），在一个验证队列（36个无OA和62个受髋OA影响的软骨）中使用qPCR对其进行了确认（P < 6.25×10-3）。我们的数据表明，细胞外基质形成失调和胶原链比例失衡可能导致髋OA的发展，SDC1可能是一个有前景的潜在治疗靶点。这些发现有助于更好地理解髋OA的分子机制，并可能有助于制定靶向治疗策略。
