Department of Anesthesiology, Qilu Hospital of Shandong University, 107 Wenhua West Road, Jinan city, 250012, Shandong, China.
Institute of Stomatology, Shandong University, 107 Wenhua West Road, Jinan city, 250012, Shandong, China.
Arthritis Res Ther. 2022 Dec 14;24(1):273. doi: 10.1186/s13075-022-02964-x.
Bone marrow-derived mesenchymal stem cells (BMSCs) are general progenitor cells of osteoblasts and adipocytes and they are characterized as a fundamental mediator for bone formation. The current research studied the molecular mechanisms underlying circRNA-regulated BMSC osteogenic differentiation.
Next-generation sequencing (NGS) was employed to study abnormal circRNA and mRNA expression in BMSCs before and after osteogenic differentiation induction. Bioinformatics analysis and luciferase reporting analysis were employed to confirm correlations among miRNA, circRNA, and mRNA. RT-qPCR, ALP staining, and alizarin red staining illustrated the osteogenic differentiation ability of BMSCs.
Data showed that circ-Iqsec1 expression increased during BMSC osteogenic differentiation. circ-Iqsec1 downregulation reduced BMSC osteogenic differentiation ability. The present investigation discovered that Satb2 played a role during BMSC osteogenic differentiation. Satb2 downregulation decreased BMSC osteogenic differentiation ability. Bioinformatics and luciferase data showed that miR-187-3p linked circ-Iqsec1 and Satb2. miR-187-3p downregulation or Satb2 overexpression restored the osteogenic differentiation capability of BMSCs post silencing circ-Iqsec1 in in vivo and in vitro experiments. Satb2 upregulation restored osteogenic differentiation capability of BMSCs post miR-187-3p overexpression.
Taken together, our study found that circ-Iqsec1 induced BMSC osteogenic differentiation through the miR-187-3p/Satb2 signaling pathway.
骨髓间充质干细胞（BMSCs）是成骨细胞和脂肪细胞的通用祖细胞，其特征是骨形成的基本介质。目前的研究旨在研究 circRNA 调控 BMSC 成骨分化的分子机制。
采用下一代测序（NGS）技术研究诱导成骨分化前后 BMSCs 中异常 circRNA 和 mRNA 的表达。利用生物信息学分析和荧光素酶报告分析验证 miRNA、circRNA 和 mRNA 之间的相关性。采用 RT-qPCR、ALP 染色和茜素红染色检测 BMSCs 的成骨分化能力。
结果表明，circ-Iqsec1 在 BMSC 成骨分化过程中表达增加。circ-Iqsec1 的下调降低了 BMSC 的成骨分化能力。本研究发现 Satb2 在 BMSC 成骨分化过程中发挥作用。Satb2 的下调降低了 BMSC 的成骨分化能力。生物信息学和荧光素酶数据表明，miR-187-3p 连接 circ-Iqsec1 和 Satb2。在体内和体外实验中，沉默 circ-Iqsec1 后，miR-187-3p 的下调或 Satb2 的过表达恢复了 BMSCs 的成骨分化能力。miR-187-3p 过表达后，Satb2 的上调恢复了 BMSCs 的成骨分化能力。
综上所述，我们的研究发现 circ-Iqsec1 通过 miR-187-3p/Satb2 信号通路诱导 BMSC 成骨分化。
