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Abstract：
Human bone marrow mesenchymal stem cells (HBMSCs) can promote new bone formation. Previous studies have proven the ability of long non-coding RNAs (lncRNAs) to modulate the osteogenic differentiation of mesenchymal stem cells. However, the molecular mechanism modulated by lncRNAs in affecting the osteogenic differentiation of HBMSCs remains largely unknown. Thus, this study aims to reveal the role of lncRNA ubiquitin-specific peptidase 2 antisense RNA 1 (USP2-AS1) in regulating the osteogenic differentiation of HBMSCs and investigate its regulatory mechanism. Through bioinformatics analysis and RT-qPCR, we confirmed that USP2-AS1 expression was increased in HBMSCs after culturing in osteogenic differentiation medium (OM-HBMSCs). Moreover, we uncovered that knockdown of USP2-AS1 inhibited the osteogenic differentiation of HBMSCs. Further exploration indicated that USP2-AS1 positively regulated the expression of its nearby gene USP2. Mechanistically, USP2-AS1 recruited lysine demethylase 3A (KDM3A) to stabilize ETS proto-oncogene 1 (ETS1), transcription factor that transcriptionally activated USP2. Additionally, USP2-induced Wnt/β-catenin signalling pathway activation via deubiquitination of β-catenin protein. In summary, our study proved that lncRNA USP2-AS1 facilitates the osteogenic differentiation of HBMSCs by targeting KDM3A/ETS1/USP2 axis to activate the Wnt/β-catenin signalling pathway.
摘要：
人骨髓间充质干细胞（HBMSCs）可以促进新骨形成。先前的研究已经证明了长链非编码RNA(lncRNA)调节间充质干细胞成骨分化的能力。然而,lncRNAs调控的影响HBMSCs成骨分化的分子机制尚不清楚。因此，本研究旨在揭示lncRNA泛素特异性肽酶2反义RNA1（USP2-AS1）在调节HBMSCs成骨分化中的作用，并探讨其调控机制。通过生物信息学分析和RT-qPCR,我们证实，在成骨分化培养基（OM-HBMSCs）中培养后，HBMSCs中USP2-AS1的表达增加。此外，我们发现USP2-AS1敲低抑制了HBMSCs的成骨分化。进一步的探索表明，USP2-AS1正调控其附近基因USP2的表达。机械上,USP2-AS1招募赖氨酸去甲基酶3A（KDM3A）以稳定ETS原癌基因1（ETS1），转录激活USP2的转录因子。此外,USP2通过β-catenin蛋白去泛素化诱导的Wnt/β-catenin信号通路激活。总之,我们的研究证明，lncRNAUSP2-AS1通过靶向KDM3A/ETS1/USP2轴激活Wnt/β-catenin信号通路，促进HBMSCs的成骨分化。
