CircRUNX2 through has-miR-203 regulates RUNX2 to prevent osteoporosis.

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.