Department of Orthopedics, Affiliated Hospital of North Sichuang Medical College, Sichuan, 637000, P. R. China.
Department of Operating Room, Affiliated Hospital of North Sichuang Medical College, Sichuan, 637000, P. R. China.
Acta Biochim Pol. 2023 Feb 25;70(1):51-57. doi: 10.18388/abp.2020_6035.
Osteoporosis, a bone disease common in the elderly, results in bone loss and damage to bone microstructure. Sirtuin 1 (Sirt1), belongs to Sirtuin family, is involved in regulating bone quality. Circ-Sirt1 is one of the transcripts of Sirt1 host gene. Here, the involvement of circ-Sirt1 was determined in bone disease for the first time, proposing that circ-Sirt1 can activate the Wnt/β-catenin pathway to promote osteogenesis differentiation. This study was aimed to elucidate the potential function of Circ-Sirt1 and Sirt1 regulatory loop in the differentiation of bone marrow mesenchymal stem cells (BMSCs). The differentiation of bone marrow mesenchymal stem cells was detected by ALP, alizarin red staining and qPCR. The dual luciferase reporter assay was applied to reveal the interaction between RNAs. The result showed that Sirt1 promoted osteogenic differentiation of BMSCs. Circ-Sirt1, derived from Sirt1, acted as miR-132 and miR-212 sponge, and up-regulated the expression of Sirt1. Furthermore, Sirt1-mediated circ-Sirt1 promoted osteogenic differentiation. Finally, we unveiled that Circ-Sirt1 facilitates osteogenic differentiation by activating the Wnt/β-catenin pathway. In conclusion, our data suggested that Circ-Sirt1 elevates osteogenic differentiation via miR-132/212/Sirt1 and Wnt/β-catenin pathway.
骨质疏松症是一种常见于老年人的骨骼疾病，导致骨量流失和骨微观结构受损。Sirtuin 1（Sirt1）属于 Sirtuin 家族，参与调节骨质量。Circ-Sirt1 是 Sirt1 宿主基因的转录本之一。在这里，Circ-Sirt1 首次被确定与骨骼疾病有关，提出 Circ-Sirt1 可以激活 Wnt/β-catenin 通路促进成骨细胞分化。本研究旨在阐明 Circ-Sirt1 和 Sirt1 调控环在骨髓间充质干细胞（BMSCs）分化中的潜在功能。通过碱性磷酸酶（ALP）、茜素红染色和 qPCR 检测骨髓间充质干细胞的分化。双荧光素酶报告基因检测用于揭示 RNA 之间的相互作用。结果表明 Sirt1 促进 BMSCs 的成骨分化。Circ-Sirt1 来源于 Sirt1，作为 miR-132 和 miR-212 的海绵体，上调 Sirt1 的表达。此外，Sirt1 介导的 Circ-Sirt1 促进成骨分化。最后，我们揭示 Circ-Sirt1 通过激活 Wnt/β-catenin 通路促进成骨分化。总之，我们的数据表明 Circ-Sirt1 通过 miR-132/212/Sirt1 和 Wnt/β-catenin 通路促进成骨分化。
