Department of Joint Bone Disease Surgery, Changhai Hospital, Navy Medical University, Shanghai 200433, P.R. China.
Department of Biostatistics and Computational Biology, School of Life Sciences, Fudan University, Shanghai 200433, P.R. China.
Cell Mol Biol (Noisy-le-grand). 2020 Sep 30;66(6):127-134.
Ankylosing spondylitis (AS) is a chronic, progressive, and inflammatory disease that mainly affects the central axis joint. Although this disease has already been well documented and studied, its pathogenesis is still not well understood. This study aimed to screen and identify key candidate genes involved in the progression of AS. For this purpose, expression profiles of GSE39340 and GSE41038 were downloaded from the Gene Expression Omnibus and displayed in the form of volcano plots and heatmaps. Differentially expressed genes (DEGs) were identified by the Limma package in R and functional enrichment analyses were performed. Moreover, STRING and Cytoscape were utilized to construct protein-protein interaction (PPI) networks and screen significant modules. Immunohistochemistry (IHC) in tissue chips of AS and normal human synovial tissues was performed to confirm the major proteins associated with its development. Western blotting (WB) and alizarin red staining were applied to validate the expression level of platelet-derived growth factor receptor beta (PDGFRB) and function during osteogenesis differentiation of fibroblasts in AS. A total of 256 DEGs were screened, including 191 up-regulated genes and 65 down-regulated genes. The enriched functions of these identified genes mainly included adherens junction, focal adhesion, and cell-substrate adherens junction. The pathways most highly associated with the progression of AS were TGF-β signaling pathway, the Hippo signaling pathway, and the AGE-RAGE signaling pathway. In addition, IHC showed that mitogen-activated protein kinase 1 (MAPK1), C-X-C motif chemokine receptor 4 (CXCR4), and PDGFRB were highly expressed in AS. PDGFRB was found upregulated during osteogenesis of fibroblasts and stimulates osteogenesis in AS. These findings may improve our understanding of the molecular mechanisms controlling AS. Pharmacological targeting of PDGFRB may initiate a possible suppression of bone formation in AS.
强直性脊柱炎（AS）是一种慢性、进行性和炎症性疾病，主要影响中轴关节。尽管这种疾病已经得到了很好的记录和研究，但它的发病机制仍不清楚。本研究旨在筛选和鉴定与 AS 进展相关的关键候选基因。为此，从基因表达综合数据库中下载了 GSE39340 和 GSE41038 的表达谱，以火山图和热图的形式显示。使用 R 中的 Limma 包识别差异表达基因（DEGs），并进行功能富集分析。此外，使用 STRING 和 Cytoscape 构建蛋白质-蛋白质相互作用（PPI）网络并筛选显著模块。对 AS 和正常人类滑膜组织的组织芯片进行免疫组织化学（IHC）检测，以验证与疾病发展相关的主要蛋白。应用 Western blot（WB）和茜素红染色验证成纤维细胞成骨分化过程中血小板衍生生长因子受体β（PDGFRB）的表达水平及其功能。筛选出 256 个 DEGs，包括 191 个上调基因和 65 个下调基因。这些鉴定基因的富集功能主要包括黏着斑、焦点黏附和细胞-基质黏着斑。与 AS 进展最相关的途径是 TGF-β信号通路、Hippo 信号通路和 AGE-RAGE 信号通路。此外，IHC 显示丝裂原活化蛋白激酶 1（MAPK1）、C-X-C 基序趋化因子受体 4（CXCR4）和 PDGFRB 在 AS 中高表达。发现 PDGFRB 在成纤维细胞的成骨过程中上调，并刺激 AS 中的成骨作用。这些发现可能有助于我们理解控制 AS 的分子机制。PDGFRB 的药物靶向可能会启动对 AS 中骨形成的抑制作用。
