Central South University, Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, Hainan, China.
Rehabilitation Medicine Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Biochem Biophys Res Commun. 2018 Jun 12;500(4):902-906. doi: 10.1016/j.bbrc.2018.04.189. Epub 2018 May 1.
Osteoarthritis (OA) is the most common form of joint disease. The development of inflammation have been considered to play a key role during the progression of OA. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, deciphering these risk regulatory pathways is critical for elucidating the mechanisms underlying OA. We constructed an OA-specific regulatory network by integrating comprehensive curated transcription and post-transcriptional resource involving transcription factor (TF) and microRNA (miRNA). To deepen our understanding of underlying molecular mechanisms of OA, we developed an integrated systems approach to identify OA-specific risk regulatory pathways. In this study, we identified 89 significantly differentially expressed genes between normal and inflamed areas of OA patients. We found the OA-specific regulatory network was a standard scale-free network with small-world properties. It significant enriched many immune response-related functions including leukocyte differentiation, myeloid differentiation and T cell activation. Finally, 141 risk regulatory pathways were identified based on OA-specific regulatory network, which contains some known regulator of OA. The risk regulatory pathways may provide clues for the etiology of OA and be a potential resource for the discovery of novel OA-associated disease genes.
骨关节炎（OA）是最常见的关节疾病。炎症的发展被认为在 OA 的进展中起关键作用。调控途径在许多致病过程中起着至关重要的作用。因此，破译这些风险调控途径对于阐明 OA 的机制至关重要。我们通过整合涉及转录因子（TF）和 microRNA（miRNA）的全面精选转录和转录后资源，构建了一个 OA 特异性调控网络。为了更深入地了解 OA 的潜在分子机制，我们开发了一种综合系统方法来识别 OA 特异性风险调控途径。在这项研究中，我们在 OA 患者的正常和炎症区域之间鉴定了 89 个差异表达的基因。我们发现 OA 特异性调控网络是一个具有小世界特性的标准无标度网络。它显著富集了许多与免疫反应相关的功能，包括白细胞分化、髓样分化和 T 细胞激活。最后，基于 OA 特异性调控网络，确定了 141 个风险调控途径，其中包含一些已知的 OA 调节剂。风险调控途径可能为 OA 的病因提供线索，并成为发现新型 OA 相关疾病基因的潜在资源。
