Departments of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China.
The Second Clinical Medical College of Nanchang University, Nanchang, 330006, Jiangxi Province, China.
Clin Rheumatol. 2024 Jan;43(1):453-464. doi: 10.1007/s10067-023-06742-1. Epub 2023 Aug 23.
Osteoarthritis (OA) is a common degenerative disease of joints, which can appear in almost any joint of the body. Therefore, the widespread occurrence of this disease has a huge impact on the lives of patients around the world. As an important part of metabolism, lipid metabolism is closely related to the occurrence and development of osteoarthritis.
We screened UGCG and KLF4 based on weighted co-expression network analysis (WGCNA) and SVM-REF analysis. The data from Gene Expression Omnibus (GEO) and single-cell data verified the expression of these two genes. We analyzed KLF4-related genes and established a diagnosis model of OA related to lipid metabolism through the least absolute shrinkage and selection operator (LASSO) analysis. RT-PCR was used to verify the expression of KLF4 in osteoarthritis.
Ten important lipid metabolism related genes (LMRGs) in OA were obtained. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that they are involve in the formation of immune microenvironment in osteoarthritis. CIBERSORT analysis revealed that there were significant differences in the immune microenvironment between osteoarthritis patients and normal controls. RT-PCR results showed that the expression of KLF4 in OA samples was lower than that in normal samples. The diagnostic model can be used to diagnose OA patients well.
Overall, we demonstrated the potential relationship between the abnormal lipid metabolism and the pathological process of OA. Finally, we identified KLF4 as our significant LMRG and constructed a KLF4-related scoring model to accurately diagnose OA. In conclusion, therapy strategies targeting on regulating lipid metabolism may become a key factor in treating OA. Key Points (a) We identified the significant LMRG KLF4 and constructed a novel KLF4-related scoring model for the accuracy diagnosis of OA. (b) The potential relationship between lipid metabolism and the immune microenvironment in OA was demonstrated in our research. (c) The relationship of lipid metabolism and OA has been further improved in our research and provided novel insight for the diagnosis and therapy for OA patients.
骨关节炎（OA）是一种常见的关节退行性疾病，几乎可以出现在身体的任何关节中。因此，这种疾病的广泛发生对全球患者的生活产生了巨大影响。作为代谢的重要组成部分，脂质代谢与骨关节炎的发生和发展密切相关。
我们基于加权共表达网络分析（WGCNA）和 SVM-REF 分析筛选了 UGCG 和 KLF4。从基因表达综合数据库（GEO）和单细胞数据中验证了这两个基因的表达。我们分析了 KLF4 相关基因，并通过最小绝对收缩和选择算子（LASSO）分析建立了一个与脂质代谢相关的 OA 诊断模型。使用 RT-PCR 验证 OA 中 KLF4 的表达。
获得了 OA 中 10 个重要的脂质代谢相关基因（LMRGs）。京都基因与基因组百科全书（KEGG）富集分析表明，它们参与了骨关节炎中免疫微环境的形成。CIBERSORT 分析显示，骨关节炎患者和正常对照之间的免疫微环境存在显著差异。RT-PCR 结果表明，OA 样本中 KLF4 的表达低于正常样本。该诊断模型可很好地用于诊断 OA 患者。
综上所述，我们证明了异常脂质代谢与 OA 病理过程之间存在潜在关系。最后，我们确定了 KLF4 作为我们的重要 LMRG，并构建了一个 KLF4 相关评分模型，以准确诊断 OA。总之，针对调节脂质代谢的治疗策略可能成为治疗 OA 的关键因素。关键点：（a）我们鉴定了重要的 LMRG KLF4，并构建了一个新的 KLF4 相关评分模型，用于 OA 的准确诊断。（b）在本研究中，我们证明了脂质代谢与 OA 中免疫微环境之间存在潜在关系。（c）本研究进一步改善了脂质代谢与 OA 的关系，为 OA 患者的诊断和治疗提供了新的见解。
