CircRNA hsa_circ_0006859 inhibits the osteogenic differentiation of BMSCs and aggravates osteoporosis by targeting miR-642b-5p/miR-483-3p and upregulating EFNA2/DOCK3

Abstract

Hsa_circ_0006859 has been found as a possible biomarker for postmenopausal osteoporosis (PMOP) with an effect on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), but the underlying mechanism is unclear. Bioinformatics analysis was used to identify dysregulated RNAs involved in osteoporosis based on public datasets. Function assays were used to determine the functions of hsa_circ_0006859 on cell proliferation and osteogenic differentiation in vitro. It was found that hsa_circ_0006859 was upregulated in OVX mice-derived BMSCs, but lowly expressed during osteogenic differentiation. Overexpressing hsa_circ_0006859 inhibited the cell proliferation and osteogenesis of BMSCs and hFOB 1.19 cells, vice versa. Bilateral ovariectomy (OVX) was used to induce PMOP in mice. The interactions among circ_0006859, miR-642b-5p/miR-483-3p, and EFNA2/DOCK3 were determined using the RIP assay. Silencing circ_0006859 relieved PMOP in mice. Mechanistically, circ_0006859 bound to miR-642b-5p/miR-483-3p directly, while miR-642b-5p and miR-483-3p respectively targeted EFNA2 and DOCK3. Hsa_circ_0006859 downregulated the expression of miR-642b-5p/miR-483-3p to upregulate EFNA2/DOCK3. Additionally, miR-642b-5p/miR-483-3p targeted EFNA2/DOCK3 to inhibit BMSCs osteogenic differentiation and facilitate osteoporosis progression by inactivating the Wnt signaling. In conclusion, hsa_circ_0006859 is involved in PMOP by targeting miR-642b-5p/EFNA2 and miR-483-3p/DOCK3 axes to maintain the Wnt-signaling pathway, which may be a novel possible therapeutic targets and biomarkers for PMOP.