Circ_0001825 promotes osteogenic differentiation in human-derived mesenchymal stem cells via miR-1270/SMAD5 axis

• Published in: Journal of orthopaedic surgery and research Vol. 18; no. 1; pp. 1 - 663
• Main Authors: Zheng, Changjun, Ding, Lingzhi, Xiang, Ziming, Feng, Mingxuan, Zhao, Fujiang, Zhou, Zhaoxin, She, Chang
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 06-09-2023; BioMed Central; BMC
• Subjects: Antibodies; Apoptosis; Bone marrow; Cell differentiation; Cell viability; Cholecystokinin; circ_0001825; Circular RNA; Flow cytometry; Fractures; Mesenchymal stem cells; MicroRNAs; miR-1270; Orthopedics; Osteogenesis; Osteogenic differentiation; Osteoporosis; Pathogenesis; Plasmids; Proteins; Smad protein; SMAD5; Smad5 protein; Stem cells; Western blotting; China; Beijing China; United States > US
• ISSN: 1749-799X; 1749-799X
• DOI: 10.1186/s13018-023-04133-5

Background The implication of deregulated circular RNAs in osteoporosis (OP) has gradually been proposed. Herein, we aimed to study the function and mechanism of circ_0001825 in OP using osteogenic-induced human-derived mesenchymal stem cells (hMSCs). Methods The content of genes and proteins was tested by quantitative real-time polymerase chain reaction and Western blotting. The osteogenic differentiation in hMSCs were evaluated by ALP activity and Alizarin Red staining, as well as the detection of osteogenesis-related markers. Cell viability and apoptosis were measured by CCK-8 assay and flow cytometry. The binding between miR-1270 and circ_0001825 or SMAD5 (SMAD Family Member 5) was confirmed by using dual-luciferase reporter assay and pull-down assay. Results Circ_0001825 was lowly expressed in OP patients and osteogenic induced hMSCs. Knockdown of circ_0001825 suppressed hMSC viability and osteogenic differentiation, while circ_0001825 overexpression showed the exact opposite effects. Mechanistically, circ_0001825/miR-1270/SMAD5 formed a feedback loop. MiR-1270 was increased and SMAD5 was decreased in OP patients and osteogenic induced hMSCs. MiR-1270 up-regulation suppressed hMSC viability and osteogenic differentiation, which was reversed by SMAD5 overexpression. Moreover, miR-1270 deficiency abolished the effects of circ_0001825 knockdown on hMSCs. Conclusion Circ_0001825 promoted hMSC viability and osteogenic differentiation via miR-1270/SMAD5 axis, suggesting the potential involvement of circ_0001825 in osteoporosis. Keywords: circ_0001825, miR-1270, SMAD5, Osteoporosis, Osteogenic differentiation