Construction of ceRNA regulatory networks for osteoporosis.

Abstract

Osteoporosis increases the risk of fracture. Improving the diagnosis and treatment of osteoporosis has clinical applications. The differentially expressed genes (DEcircRs, DEmRs, DEmiRs) of osteoporotic patients and controls were analyzed using the GEO database, and enrichment analysis of DEmRs was performed. circRNAs and mRNAs, which were predicted to have a target relationship with DEmRs, were obtained to compare competing endogenous RNA (ceRNA) regulatory networks by comparison with differentially expressed genes. Molecular experiments were utilized to validate the expression of genes within the network. The interactions between genes within the ceRNA network were validated by luciferase reporter assays. Following overexpression of circ_0070304 in bone marrow mesenchymal stem cells (BMSCs), the osteogenic differentiation of the cells was assessed by Alizarin Red staining. A total of 110 intersectional DEmRs between patients with osteoporosis and controls from GSE35958 and GSE56815, which were mainly enriched in estrogen, the thyroid hormone signaling pathway, and adherens junctions were identified. A ceRNA network [circ_0070304/miR‑183‑5p/ring finger and CCCH‑type domains 2 (RC3H2)] was then constructed. Circ_0070304 acted as a sponge for miR‑183‑5p and regulated RC3H2 expression. Overexpression of circ_0070304 upregulated ROCK1 and induced osteogenic differentiation. The ceRNA regulatory network that was obtained is expected to be a new target for osteoporosis treatment and to provide new insights into the diagnosis and treatment of osteoporosis in greater depth.