CircRUNX2 through has‐miR‐203 regulates RUNX2 to prevent osteoporosis

• Published in: Journal of cellular and molecular medicine 2018-12, Vol.22 (12), p.6112-6121
• Main Authors: Yin, Qudong, Wang, Jian, Fu, Qiang, Gu, Sanjun, Rui, Yongjuan
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; Biotin; Bone Marrow Cells - metabolism; Cbfa-1 protein; Cell Differentiation - genetics; Cell-Free Nucleic Acids - blood; circRUNX2; Core Binding Factor Alpha 1 Subunit - blood; Core Binding Factor Alpha 1 Subunit - genetics; Femur; Gene Expression Regulation; Humans; Mesenchymal Stem Cells - metabolism; Mesenchyme; MicroRNAs - blood; MicroRNAs - genetics; MiR‐203; Original; Osteoblasts - metabolism; Osteogenesis - genetics; Osteoporosis; Osteoporosis - blood; Osteoporosis - genetics; Osteoporosis - pathology; Proteins; Ribonucleic acid; RNA; RNA, Long Noncoding - blood; RNA, Long Noncoding - genetics; RUNX2; Stem cells; Tissues
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.13888

Objective We aimed to discover the molecular mechanism of hsa_circ_0076694 (circRUNX2) on osteogenic differentiation. We also explored the interaction between circRUNX2, miR‐203 and RUNX2. Methods Clinical samples obtained from femoral neck fracture patients’ bone tissues were used to collect circRUNX2, miR‐203, and RUNX2 expression data, while their expression changes were observed in human bone mesenchymal stem cells (hBMSCs) during osteogenic differentiation. QRT‐PCR and Western blot were used to analyse levels of RNAs and proteins. Biotin pull down, RIP, RNA FISH, and Dual‐Luciferase Reporter assays demonstrated the relationship between circRUNX2, miR‐203, and RUNX2. ALP and ARS staining were used to measure the degree of osteogenic differentiation under the control of circRUNX2, miR‐203. Results CircRUNX2 were down‐regulated in osteoporotic patients’ bone tissues. CircRUNX2 could inhibit miR‐203 expression by sponging miR‐203. MiR‐203 inhibited osteogenic differentiation by targeting the 3′‐UTR of RUNX2 and down‐regulate RUNX2 expression. Overexpression of circRUNX2 promoted the expression of osteogenic differentiation‐related proteins such as RUNX2, OCN, OPN, BSP, and prevented osteoporosis. Conclusion circRUNX2 could sponge miR‐203 and enhance RUNX2 expression, thus circRUNX2 prevents osteoporosis and may provide a novel therapeutic strategy for it.