Department of Veterinary Medicine, Laboratory of Veterinary Surgery, College of Bioresource and Sciences, Nihon University, Fujisawa, Kanagawa, Japan.
PLoS One. 2021 Jan 28;16(1):e0246188. doi: 10.1371/journal.pone.0246188. eCollection 2021.
Osteoarthritis (OA) is one of the major causes of chronic pain in dogs. However, the pathogenesis of OA has not been fully understood in dogs. The objective of this study was to comprehensively investigate the mRNA expression levels of proinflammatory cytokines, inflammatory mediators, nerve growth factor and its receptor, and matrix metalloproteinases in the synovium of dogs with spontaneous OA as well as to elucidate their relationships with the severity of synovitis. Dogs that were diagnosed with stifle OA on the basis of radiographic findings were included, and the degree of synovitis was observed using stifle arthroscopy. The dogs were assigned to two different groups depending on their synovitis scores: the low-grade group (score of 1 or 2; n = 8) and high-grade group (score of 3 to 5; n = 18). The dogs showing no evidence of orthopedic disease were included in the control group (n = 6). Synovial tissue samples were collected from the sites at which synovitis scores were assessed using arthroscopy. Total RNA was extracted from the collected synovial tissue, and cDNA was synthesized. Subsequently, RT-qPCR were performed using canine-specific primer sets for IL1B, IL6, CXCL8, TNF, TGFB1, PTGS2, PTGES, MMP3, MMP13, NGF, NTRK1, and PTGER4. Expression levels of IL1B, IL6, CXCL8, and MMP13 were significantly higher in the high-grade group than in the control group. In addition, expression levels of IL1B, CXCL8, TNF, and PTGS2 were significantly higher in the high-grade group than in the low-grade group. Expression levels of IL1B, IL6, CXCL8, TNF, PTGS2, and PTGER4 showed significant positive correlation with synovitis score. In conclusion, all mRNA expression levels in the synovial membrane varied according to the degree of synovitis in dogs with spontaneous OA. Thus, this study may partially elucidate the pathogenesis of synovitis in dogs with spontaneous OA.
骨关节炎（OA）是导致犬慢性疼痛的主要原因之一。然而，OA 的发病机制在犬中尚未完全阐明。本研究的目的是全面研究自发性 OA 犬滑膜中促炎细胞因子、炎症介质、神经生长因子及其受体和基质金属蛋白酶的 mRNA 表达水平，并阐明它们与滑膜炎严重程度的关系。根据放射学发现诊断为膝关节 OA 的犬被纳入研究，通过膝关节镜观察滑膜炎程度。根据滑膜炎评分将犬分为两组：低级别组（评分 1 或 2；n = 8）和高级别组（评分 3 至 5；n = 18）。未表现出骨科疾病迹象的犬被纳入对照组（n = 6）。使用关节镜评估滑膜炎评分的部位采集滑膜组织样本。从收集的滑膜组织中提取总 RNA，并合成 cDNA。随后，使用犬特异性引物对 IL1B、IL6、CXCL8、TNF、TGFB1、PTGS2、PTGES、MMP3、MMP13、NGF、NTRK1 和 PTGER4 进行 RT-qPCR。高级别组的 IL1B、IL6、CXCL8 和 MMP13 的表达水平明显高于对照组。此外，高级别组的 IL1B、CXCL8、TNF 和 PTGS2 的表达水平明显高于低级别组。IL1B、IL6、CXCL8、TNF、PTGS2 和 PTGER4 的表达水平与滑膜炎评分呈显著正相关。综上所述，自发性 OA 犬滑膜中所有 mRNA 表达水平均根据滑膜炎程度而变化。因此，本研究可能部分阐明了自发性 OA 犬滑膜炎的发病机制。
