%0 Journal Article
%T CircZfp644-205 inhibits osteoblast differentiation and induces apoptosis of pre-osteoblasts via sponging miR-455-3p and promoting SMAD2 expression.
%A Zhang P
%A Liu J
%A Chai Z
%A Fu J
%A Li S
%A Yang Z
%J Eur J Med Res
%V 29
%N 1
%D 2024 Jun 8
%M 38849933
%F 4.981
%R 10.1186/s40001-024-01903-7
%X <B>BACKGROUND: </B>Circular RNAs (circRNAs) are involved in the progression of osteoporosis; however, their impact on osteogenic differentiation has yet to be fully elucidated. In this study, we identified a novel circRNA known as circZfp644-205 and investigated its effect on osteogenic differentiation and apoptosis in osteoporosis.<BR><B>METHODS: </B>CircZfp644-205, miR-445-3p, and SMAD2 levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). MC3T3-E1 cells were subjected to microgravity (MG) to establish a cell model. Osteogenic differentiation was assessed using qRT-PCR, Alizarin Red S staining, alkaline phosphatase staining, and western blot. The apoptosis was evaluated using flow cytometry. The relationship between miR-445-3p and circZfp644-205 or SMAD2 was determined using bioinformatics, RNA pull-down, and luciferase reporter assay. Moreover, a hindlimb unloading mouse model was generated to investigate the role of circZfp644-205 in vivo using Micro-CT.<BR><B>RESULTS: </B>CircZfp644-205 expression was up-regulated significantly in HG-treated MC3T3-E1 cells. Further in vitro studies confirmed that circZfp644-205 knockdown inhibited the osteogenic differentiation and induced apoptosis of pre-osteoblasts. CircZfp644-205 acted as a sponge for miR-455-3p, which reversed the effects of circZfp644-205 on pre-osteoblasts. Moreover, miR-455-3p directly targeted SMAD2, thus inhibiting the expression of SMAD2 to regulate cellular behaviors. Moreover, circZfp644-205 alleviated the progression of osteoporosis in mice.<BR><B>CONCLUSIONS: </B>This study provides a novel circRNA that may serve as a potential therapeutic target for osteoporosis and expands our understanding of the molecular mechanism underlying the progression of osteoporosis.