Long noncoding RNAs (lncRNAs), which serve as important and powerful regulators of various biological activities, have gained widespread attention in recent years. Emerging evidence has shown that some lncRNAs play important regulatory roles in osteoblast differentiation of mesenchymal stem cells (MSCs), suggesting a potential therapeutic strategy for bone fracture. As a recently identified lncRNA, linc-ROR was reported to mediate the reprogramming ability of differentiated cells into induced pluripotent stem cells (iPSCs) and human embryonic stem cells (ESCs) self-renewal. However, other functions of linc-ROR remain elusive. In this study, linc-ROR was found to be upregulated during osteogenesis of human bone-marrow-derived MSCs. Ectopic expression of linc-ROR significantly accelerated, whereas knockdown of linc-ROR suppressed, osteoblast differentiation. Using bioinformatic prediction and luciferase reporter assays, we demonstrated that linc-ROR functioned as a microRNA (miRNA) sponge for miR-138 and miR-145, both of which were negative regulators of osteogenesis. Further investigations revealed that linc-ROR antagonized the functions of these two miRNAs and led to the de-repression of their shared target ZEB2, which eventually activated Wnt/β-catenin pathway and hence potentiated osteogenesis. Taken together, linc-ROR modulated osteoblast differentiation by acting as a competing endogenous RNA (ceRNA), which may shed light on the functional characterization of lncRNAs in coordinating osteogenesis.

长的非编码RNA（lncRNA），作为各种生物活动的重要而有力的调节者，近年来受到了广泛的关注。新兴证据表明，某些lncRNA在间充质干细胞（MSC）的成骨细胞分化中起重要的调节作用，这提示了潜在的骨折治疗策略。作为最近鉴定出的lncRNA，据报道，linc-ROR介导分化细胞向诱导多能干细胞（iPSC）和人类胚胎干细胞（ESC）自我更新的重编程能力。但是，linc-ROR的其他功能仍然难以捉摸。在这项研究中，发现linc-ROR在人骨髓来源的MSC的成骨过程中被上调。linc-ROR的异位表达明显加速，而linc-ROR的敲低则受到抑制，成骨细胞分化。使用生物信息学预测和萤光素酶报告基因检测，我们证明了linc-ROR充当miR-138和miR-145的microRNA（miRNA）海绵，它们都是成骨作用的负调控因子。进一步的研究表明，linc-ROR拮抗了这两个miRNA的功能，并导致其共同靶标ZEB2的抑制，最终激活了Wnt /β-catenin途径，从而增强了成骨作用。两者合计，linc-ROR通过充当竞争性内源RNA（ceRNA）来调节成骨细胞分化，这可能为lncRNA在协调成骨过程中的功能表征提供了启示。两者都是成骨作用的负调节剂。进一步的研究表明，linc-ROR拮抗了这两个miRNA的功能，并导致其共同靶标ZEB2的抑制，最终激活了Wnt /β-catenin途径，从而增强了成骨作用。两者合计，linc-ROR通过充当竞争性内源RNA（ceRNA）来调节成骨细胞分化，这可能为lncRNA在协调成骨过程中的功能表征提供了启示。两者都是成骨作用的负调节剂。进一步的研究表明，linc-ROR拮抗了这两个miRNA的功能，并导致其共同靶标ZEB2的抑制，最终激活了Wnt /β-catenin途径，从而增强了成骨作用。两者合计，linc-ROR通过充当竞争性内源RNA（ceRNA）来调节成骨细胞分化，这可能为lncRNA在协调成骨过程中的功能表征提供了启示。