hsa_circ_0004276 inhibits osteogenic differentiation of bone marrow mesenchymal stem cells and exacerbates postmenopausal osteoporosis through interaction with ELAVL1.

OBJECTIVE: The aim of this study was to investigate the potential of hsa_circ_0004276 as a diagnostic marker for Postmenopausal Osteoporosis (PMO) and its potential interaction with the RNA-binding protein ELAV-like RNA binding protein-1 (ELAVL1). METHODS: The circRNA expression profiles obtained from the GSE159121 dataset were used to screen for differentially expressed circRNAs in patients with PMO. hsa_circ_0004276 was further analyzed and validated for its circular structure using a bioinformatics website, actinomycin D, and RNase R assays. Serum samples from 115 PMO patients and 103 healthy controls were collected. RT-qPCR and western blot were applied to assess hsa_circ_0004276 and ELAVL1. The effects of hsa_circ_0004276 and ELAVL1 on osteogenic differentiation of human Bone Marrow Mesenchymal Stem Cells (BMSCs) were investigated by in vitro experiments. RESULTS: hsa_circ_0004276 was highly expressed in PMO patients and negatively correlated with low bone mineral density. hsa_circ_0004276 had high specificity and sensitivity for the diagnosis of PMO. hsa_circ_0004276 significantly interacted with ELAVL1. During BMSC osteogenic differentiation, hsa_circ_0004276 knockdown significantly increased calcium deposition and ALP activity, while hsa_circ_0004276 overexpression showed the opposite effect. In addition, ELAVL1 expression was reduced in PMO patients and positively correlated with hsa_circ_0004276. CONCLUSION: hsa_circ_0004276 regulates osteogenic differentiation of BMSCs through its interaction with ELAVL1 in PMO pathogenesis. This finding provides a new perspective for the study of the molecular mechanism of PMO and a theoretical basis for the development of new therapeutic targets.