Human adipose-derived stem cells (hASCs) are a promising cell type for bone tissue regeneration. Circular RNAs (circRNAs) have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis. However, how circRNAs regulate hASCs in osteogenesis is still unclear. Herein, we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs. Knockdown of circ_0003204 by siRNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs. We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p. We predicted and confirmed that miR-370-3p had targets in the 3′-UTR of HDAC4 mRNA. The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis. Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model, while overexpression of circ_0003204 inhibited bone defect repair. Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.

人类脂肪干细胞 (hASCs) 是一种很有前途的骨组织再生细胞类型。环状 RNA (circRNA) 已被证明在调节各种细胞分化和参与间充质干细胞成骨中起关键作用。然而，circRNAs如何在成骨过程中调节hASCs仍不清楚。在此，我们发现 circ_0003204 在 hASCs 的成骨分化过程中显着下调。通过 siRNA 敲低 circ_0003204 或通过慢病毒过表达证实 circ_0003204 可以负调节 hASCs 的成骨分化。我们进行了双荧光素酶报告测定和拯救实验，以验证 circ_0003204 通过海绵化 miR-370-3p 调节成骨分化。我们预测并证实了 miR-370-3p 在 HDAC4 mRNA 的 3'-UTR 中有靶标。以下拯救实验表明circ_0003204通过miR-370-3p/HDAC4轴调节hASCs的成骨分化。随后的体内实验表明，在小鼠骨缺损模型中，circ_0003204 的沉默增加了骨形成并促进了成骨相关蛋白的表达，而 circ_0003204 的过表达抑制了骨缺损修复。我们的研究结果表明，circ_0003204 可能是促进 hASCs 修复骨缺损疗效的有希望的靶点。而circ_0003204的过表达抑制骨缺损修复。我们的研究结果表明，circ_0003204 可能是促进 hASCs 修复骨缺损疗效的有希望的靶点。而circ_0003204的过表达抑制骨缺损修复。我们的研究结果表明，circ_0003204 可能是促进 hASCs 修复骨缺损疗效的有希望的靶点。