Department of Orthopedics, The Third Affiliated Hospital of Anhui Medical University (The First People's Hospital of Hefei), Hefei, Anhui, China (mainland).
Med Sci Monit. 2024 Jun 15;30:e943369. doi: 10.12659/MSM.943369.
BACKGROUND Osteoarthritis (OA) is a chronic degenerative disease characterized by synovitis and has been implicated in sphingolipid metabolism disorder. However, the role of sphingolipid metabolism pathway (SMP)-related genes in the occurrence of OA and synovial immune dysregulation remains unclear. MATERIAL AND METHODS In this study, we obtained synovium-related databases from GEO (n=40 for both healthy controls and OA) and analyzed the expression levels of SMP-related genes. Using 2 algorithms, we identified hub genes and developed a diagnostic model incorporating these hub genes to predict the occurrence of OA. Subsequently, the hub genes were further validated in peripheral blood samples from OA patients. Additionally, CIBERSORT and MCP-counter analyses were employed to explore the correlation between hub genes and immune dysregulation in OA synovium. WGCNA was used to determine enriched modules in different clusters. RESULTS Overall, the expression levels of SMP genes were upregulated in OA synovium. We identified 6 hub genes of SMP and constructed an excellent diagnostic model (AUC=0.976). The expression of re-confirmed hub genes showed associations with immune-related cell infiltration and levels of inflammatory cytokines. Furthermore, we observed heterogeneity in the expression patterns of hub genes across different clusters of OA. Notably, older patients displayed increased susceptibility to elevated levels of pain-related inflammatory cytokines and infiltration of immune cells. CONCLUSIONS The SMP-related hub genes have the potential to serve as diagnostic markers for OA patients. Moreover, the 4 hub genes of SMP demonstrate wide participation in immune dysregulation in OA synovium. The activation of different pathways is observed among different populations of patients with OA.
骨关节炎（OA）是一种以滑膜炎为特征的慢性退行性疾病，其发病机制与鞘脂代谢紊乱有关。然而，鞘脂代谢途径（SMP）相关基因在 OA 发病及滑膜免疫失调中的作用尚不清楚。
本研究从 GEO 数据库中获取滑膜相关数据库（健康对照组和 OA 组各 40 例），分析 SMP 相关基因的表达水平。使用 2 种算法，鉴定枢纽基因并建立包含这些枢纽基因的诊断模型，以预测 OA 的发生。随后，在 OA 患者的外周血样本中进一步验证枢纽基因。此外，还采用 CIBERSORT 和 MCP-counter 分析来探讨 OA 滑膜中枢纽基因与免疫失调的相关性。使用 WGCNA 确定不同聚类中富集的模块。
OA 滑膜中 SMP 基因的表达总体上调。我们确定了 SMP 的 6 个枢纽基因，并构建了一个优秀的诊断模型（AUC=0.976）。经重新验证的枢纽基因的表达与免疫相关细胞浸润和炎症细胞因子水平相关。此外，我们观察到 OA 不同聚类中枢纽基因的表达模式存在异质性。值得注意的是，老年患者对疼痛相关炎症细胞因子水平升高和免疫细胞浸润的易感性增加。
SMP 相关枢纽基因有望成为 OA 患者的诊断标志物。此外，SMP 的 4 个枢纽基因广泛参与 OA 滑膜中的免疫失调。不同 OA 患者群体中观察到不同途径的激活。
