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circCacna1c modulates osteogenic differentiation of BMSCs via miR-7669-3p/Ciart axis in osteoporosis
Zhipeng Chen1, Yan Li2, Bailing Chen3
1Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong province, 510000, People's Republic of China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong province, 510000, People's Republic of China; Department of Spine Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong province, 510000, People's Republic of China.
Abstract:
Osteoporosis is a prevalent disorder characterized by reduced bone mass and deterioration of bone microstructure, leading to an increased risk of fractures. The osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) plays a critical role in bone formation. Circular RNAs (circRNAs) have been implicated in various diseases, including osteoporosis, by modulating gene expression. This study explores the role of circCacna1c in osteogenic differentiation and its potential as a therapeutic target for osteoporosis. CircCacna1c expression was downregulated in OVX mice and upregulated during osteogenic differentiation of BMSCs. Overexpression of circCacna1c promoted osteogenesis by increasing key osteogenic markers, such as Runx2, Ocn, and Alp. CircCacna1c was found to act as a molecular sponge for miR-7669-3p, which targets Ciart, enhancing its expression. The miR-7669-3p/Ciart axis played a crucial role in osteogenic differentiation, with knockdown of Ciart reversing the osteogenic-promoting effects of circCacna1c. In conclusions, the circCacna1c/miR-7669-3p/Ciart pathway is involved in regulating the osteogenic differentiation of BMSCs and may serve as a potential therapeutic target for osteoporosis. Modulating circCacna1c expression or its downstream signaling could offer novel strategies for the treatment and management of osteoporosis.
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