运用网络药理学方法探讨塞来昔布治疗异位骨化的有效靶点。通过检索GEO和CTD数据库并进行交叉，获得与异位骨化相关的潜在分子。塞来昔布的潜在结合靶点是从 STITCH 数据库中获得的。使用 STRING 数据库在塞来考昔的潜在结合靶点和异位骨化的潜在相关分子之间构建了蛋白质-蛋白质相互作用网络。使用R软件中的GO和KEGG富集分析进一步分析蛋白质-蛋白质相互作用网络中的分子，然后对塞来昔布-异位骨化目标数据集中的活性分子进行富集分析。根据蛋白质-蛋白质相互作用网络内的“程度”值和富集度来选择中心基因。使用分子对接技术观察中心基因与塞来昔布的结合亲和力。最后，进行体外实验来验证枢纽基因的有效性并探讨其在异位骨化进展中的调节作用。此外，还研究了调节枢纽基因表达的塞来昔布在异位骨化治疗中的治疗效果。鉴定了 568 个与异位骨化相关的潜在分子和塞来昔布的 76 个潜在结合靶点。交叉后得到13个塞来昔布治疗异位骨化的潜在功能分子。 KEGG分析表明类风湿性关节炎、NF-κB信号通路、癌症中的通路、抗叶酸耐药性、癌症中的MicroRNA等通路在塞来昔布治疗异位骨化中发挥作用。对 13 个潜在功能分子的进一步富集分析确定了 5 个中心基因：IL6、CCND1、PTGS2、IGFBP3、CDH1。分子对接结果表明塞来昔布与5个hub基因中的CCND1表现出优异的结合亲和力。实验验证发现，CCND1在异位骨化进展过程中高表达，早期促进异位骨化，后期抑制异位骨化，塞来昔布治疗异位骨化依赖于CCND1。在塞来昔布治疗异位骨化过程中，免疫和炎症信号通路发挥着重要作用。塞来昔布对异位骨化的治疗作用取决于枢纽基因CCND1，该基因在异位骨化进展的不同阶段发挥不同的作用，最终抑制异位骨化的发生。© 2024 The Authors.

To explore the effective targets of Celecoxib in the treatment of heterotopic ossification using network pharmacology methods.Potential molecules related to heterotopic ossification were obtained by retrieving the GEO and CTD databases and intersecting them. Potential binding targets of Celecoxib were acquired from the STITCH database. A protein-protein interaction network was constructed between potential binding targets of Celecoxib and potential related molecules of heterotopic ossification using the STRING database. Molecules in the protein-protein interaction network were further analyzed using GO and KEGG enrichment analysis in R software, followed by enrichment analysis of active molecules in the Celecoxib-heterotopic ossification target dataset. Hub genes were selected based on the "degree" value and enrichment within the protein-protein interaction network. The binding affinity of hub genes to Celecoxib was observed using molecular docking techniques. Finally, in vitro experiments were conducted to validate the effectiveness of hub genes and explore their regulatory role in the progression of heterotopic ossification. Additionally, the therapeutic effect of Celecoxib, which modulates the expression of the hub genes, was investigated in the treatment of heterotopic ossification.568 potential molecules related to heterotopic ossification and 76 potential binding targets of Celecoxib were identified. After intersection, 13 potential functional molecules in Celecoxib's treatment of heterotopic ossification were obtained. KEGG analysis suggested pathways such as Rheumatoid arthritis, NF-kappa B signaling pathway, Pathways in cancer, Antifolate resistance, MicroRNAs in cancer play a role in the treatment of heterotopic ossification by Celecoxib. Further enrichment analysis of the 13 potential functional molecules identified 5 hub genes: IL6, CCND1, PTGS2, IGFBP3, CDH1. Molecular docking results indicated that Celecoxib displayed excellent binding affinity with CCND1 among the 5 hub genes. Experimental validation found that CCND1 is highly expressed in the progression of heterotopic ossification, promoting heterotopic ossification in the early stages and inhibiting it in the later stages, with Celecoxib's treatment of heterotopic ossification depending on CCND1.In the process of treating heterotopic ossification with Celecoxib, immune and inflammatory signaling pathways play a significant role. The therapeutic effect of Celecoxib on heterotopic ossification depends on the hub gene CCND1, which plays different roles at different stages of the progression of heterotopic ossification, ultimately inhibiting the occurrence of heterotopic ossification.© 2024 The Authors.