Department of Orthopedic Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Aging (Albany NY). 2022 Apr 19;14(8):3400-3415. doi: 10.18632/aging.204018.
Circular RNA (circRNA) is related to many human diseases including osteoarthritis (OA). Our research purpose was to show that functional circRNAs have a role in the pathogenesis of OA, while also identifying potential circRNA that bind to miRNA-27b-3p. Microarray analysis was used to evaluate the expression of CircRNA in OA and normal cartilage. The role and functional mechanism of Circ_0000423 up-regulation were detected in OA and verified and . RNA transfection, qRT-PCR, Western blot analysis, immunofluorescence, and dual-luciferase assays were used to investigate the interaction between Circ_0000423 and miRNA-27b-3p . The roles of Circ_0000423 were discussed . Our results discovered 11 down-regulated circRNAs and 101 up-regulated circRNAs between control and OA tissues, and confirmed that Circ_0000423 an increase significantly in OA tissues by evaluating the different circRNAs expressions. Meanwhile, luciferase analysis confirmed Circ_0000423 can be directly targeted by miRNA-27b-3p and act as a miRNA-27b-3p sponge. Circ_0000423 can influence MMP-13 and collagen II expression by targeting miRNA-27b-3p expression as ceRNA in OA. Furthermore, AAV-shRNA-Circ 0000423 intra-articular injection slows the progression of OA by decreasing articular cartilage destruction and erosion, joint surface fibrosis, osteophyte formation, MMP-13 expression, and increasing collagen II expression in the articular cartilage of ACLT-induced OA mice model. These findings confirmed that the Circ_0000423-miRNA-27b-3p-MMP-13 axis could affect the pathogenesis of OA which might lead to a novel target for diagnostic molecular biological indicators and potential OA treatments.
环状 RNA (circRNA) 与许多人类疾病有关,包括骨关节炎 (OA)。我们的研究目的是表明功能性 circRNA 在 OA 的发病机制中起作用,同时鉴定潜在的与 miRNA-27b-3p 结合的 circRNA。微阵列分析用于评估 OA 和正常软骨中 CircRNA 的表达。检测 Circ_0000423 上调在 OA 中的作用和功能机制,并在 OA 中进行验证。使用 RNA 转染、qRT-PCR、Western blot 分析、免疫荧光和双荧光素酶测定来研究 Circ_0000423 与 miRNA-27b-3p 之间的相互作用。讨论 Circ_0000423 的作用。我们的结果发现,在对照和 OA 组织之间有 11 个下调的 circRNA 和 101 个上调的 circRNA,通过评估不同 circRNA 的表达,证实 Circ_0000423 在 OA 组织中显著增加。同时,荧光素酶分析证实 Circ_0000423 可被 miRNA-27b-3p 直接靶向,并作为 miRNA-27b-3p 的海绵。Circ_0000423 可通过靶向 miRNA-27b-3p 表达作为 ceRNA 影响 OA 中 MMP-13 和胶原 II 的表达。此外,AAV-shRNA-Circ 0000423 关节内注射通过减少关节软骨破坏和侵蚀、关节面纤维化、骨赘形成、MMP-13 表达和增加 ACLT 诱导的 OA 小鼠模型中关节软骨的胶原 II 表达来减缓 OA 的进展。这些发现证实 Circ_0000423-miRNA-27b-3p-MMP-13 轴可能影响 OA 的发病机制,这可能为诊断分子生物学指标和潜在的 OA 治疗提供新的靶点。