长链非编码 RNA MEG3 通过靶向 miR-93/TGFBR2 轴抑制骨关节炎软骨细胞细胞外基质的降解。
LncRNA MEG3 Inhibits the Degradation of the Extracellular Matrix of Chondrocytes in Osteoarthritis via Targeting miR-93/TGFBR2 Axis.
机构信息
Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
Department of Orthopedics, Yancheng City No. 1 People's Hospital, Yancheng, People's Republic of China.
出版信息
Cartilage. 2021 Dec;13(2_suppl):1274S-1284S. doi: 10.1177/1947603519855759. Epub 2019 Jun 28.
BACKGROUND
As a degenerative joint disease, osteoarthritis (OA) is characterized by articular cartilage degradation. Long noncoding RNAs (lncRNAs) act critical roles in the regulation of OA development, including affecting the proliferation, apoptosis, extracellular matrix (ECM) degradation, and inflammatory response of chondrocytes. The current study's aim was to investigate the regulatory function and the underlying molecular mechanism of lncRNA MEG3 in ECM degradation of chondrocytes in OA.
METHODS
In the current study, chondrocytes were induced by interleukin-1β (IL-1β) to simulate OA condition, and further assessed cell viability, lncRNA MEG3 and miR-93 expression levels. Overexpression or knockdown of lncRNA MEG3 in chondrocytes treated with IL-1β were performed to investigate the function of MEG3 in regulating cell proliferation, apoptosis and ECM degradation using EdU assay, flow cytometry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot. The interaction between MEG3 and miR-93 was assessed using qRT-PCR. Furthermore, overexpression of miR-93 was performed as recovery experiment to explore the functional mechanism of MEG3.
RESULTS
MEG3 was significantly downregulated in chondrocytes treated with IL-1β, whereas miR-93 was upregulated concomitantly. Overexpression of MEG3 induced the proliferation, suppressed the apoptosis, and relieved the degradation of ECM in IL-1β-induced chondrocytes. By contrast, knockdown of MEG3 suppressed the proliferation, promoted the apoptosis, and aggravated ECM degradation in IL-1β induced chondrocytes. In addition, MEG3 was found to relieve the inhibitive expression of TGFBR2 as a competitive endogenous RNA (ceRNA) of miR-93, and then activated transforming growth factor-β (TGF-β) signaling pathway, regulated chondrocytes ECM degradation in IL-1β induced chondrocytes subsequently.
CONCLUSION
LncRNA MEG3 targeted miR-93/TGFBR2 axis, regulated the proliferation, apoptosis and ECM degradation of chondrocytes in OA.
背景
骨关节炎（OA）作为一种退行性关节疾病，其特征在于关节软骨降解。长链非编码 RNA（lncRNA）在 OA 发展的调控中发挥着关键作用，包括影响软骨细胞的增殖、凋亡、细胞外基质（ECM）降解和炎症反应。本研究旨在探讨 lncRNA MEG3 在 OA 软骨细胞 ECM 降解中的调控作用及其潜在的分子机制。
方法
本研究中，通过白细胞介素-1β（IL-1β）诱导软骨细胞，模拟 OA 状态，进一步评估细胞活力、lncRNA MEG3 和 miR-93 的表达水平。在 IL-1β 处理的软骨细胞中过表达或敲低 lncRNA MEG3，通过 EDU 检测、流式细胞术、实时定量逆转录聚合酶链反应（qRT-PCR）和 Western blot 检测 MEG3 调节细胞增殖、凋亡和 ECM 降解的功能。通过 qRT-PCR 评估 MEG3 与 miR-93 的相互作用。此外，进行 miR-93 的过表达作为恢复实验，以探讨 MEG3 的功能机制。
结果
IL-1β 处理的软骨细胞中 MEG3 表达显著下调，而 miR-93 表达同时上调。MEG3 的过表达诱导增殖，抑制凋亡，并缓解 IL-1β 诱导的软骨细胞 ECM 降解。相反，MEG3 的敲低抑制增殖，促进凋亡，并加重 IL-1β 诱导的软骨细胞 ECM 降解。此外，作为 miR-93 的竞争性内源性 RNA（ceRNA），MEG3 被发现可以缓解 TGFBR2 的抑制表达，从而激活转化生长因子-β（TGF-β）信号通路，调节 IL-1β 诱导的软骨细胞 ECM 降解。
结论
lncRNA MEG3 通过靶向 miR-93/TGFBR2 轴，调节 OA 软骨细胞的增殖、凋亡和 ECM 降解。
Zotero 插件