Circ-Sirt1 promotes osteoblast differentiation by activating Sirt1 and Wnt/β-catenin pathway

Abstract

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.