Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
Southeast University, Nanjing, China.
PeerJ. 2023 Aug 14;11:e15791. doi: 10.7717/peerj.15791. eCollection 2023.
This investigation sought to elucidate promising treatment modalities for rotator cuff tears (RCTs) by delving into the molecular machinations instigating the affliction. The focus was on differentially expressed genes (DEGs) linked to RCTs, and the exploration of their roles and operative pathways.
DEGs were discerned from GEO datasets, followed by the establishment of a protein-protein interaction (PPI) network. Subsequently, the network's core genes were determined employing a Venn diagram. Enrichment analysis facilitated the unveiling of the biological roles and signal transduction pathways of these pivotal genes, thus shedding light on molecular strategies for RCT-targeted treatment. The Discovery Studio 2019 software was employed to sift through FDA-sanctioned drugs targeting these essential proteins. Moreover, the efficaciousness of these FDA-endorsed drugs vis-à-vis RCTs was corroborated by the construction of an animal model of the injury and the cultivation of tendon-derived stem cells.
Bioinformatics outcomes revealed a significant overexpression of S100A1 and RASSF8 in RCT patients. The FDA drug repository indicated that Butanediamide has a selective affinity for S100A1 and RASSF8. Subsequent and experimentation demonstrated that Butanediamide could suppress S100A1 expression and bolster TDSC proliferation, thereby facilitating RCT healing.
S100A1 and RASSF8 are pivotal genes implicated in RCTs, and their roles have been elucidated. The FDA-approved compound, Butanediamide, may represent a prospective therapeutic agent for RCTs by targeting S100A1 and RASSF8, respectively.
本研究旨在深入探讨引发肩袖撕裂（RCT）的分子机制，以寻找有前途的治疗方法。研究重点是与 RCT 相关的差异表达基因（DEGs），并探讨它们的作用和作用途径。
从 GEO 数据集识别 DEGs，然后建立蛋白质-蛋白质相互作用（PPI）网络。接下来，使用 Venn 图确定网络的核心基因。富集分析揭示了这些关键基因的生物学功能和信号转导途径，从而为针对 RCT 的治疗提供了分子策略。使用 Discovery Studio 2019 软件筛选针对这些关键蛋白的 FDA 批准药物。此外，通过构建损伤动物模型和培养肌腱衍生干细胞，验证了这些 FDA 批准药物治疗 RCT 的有效性。
生物信息学结果表明，RCT 患者中 S100A1 和 RASSF8 表达显著上调。FDA 药物库表明丁二酰胺对 S100A1 和 RASSF8 具有选择性亲和力。进一步的实验表明，丁二酰胺可以抑制 S100A1 的表达并促进 TDSC 的增殖，从而促进 RCT 的愈合。
S100A1 和 RASSF8 是与 RCT 相关的关键基因，其作用已被阐明。FDA 批准的化合物丁二酰胺可能通过靶向 S100A1 和 RASSF8 分别成为 RCT 的潜在治疗药物。
