Background/Aims: Circular RNAs (circRNAs) serve as potential diagnostic biomarkers. In this study, we aimed to identify a potential biomarker from peripheral blood mononuclear cells (PBMCs) of patients with postmenopausal osteoporosis (PMOP). Methods: CircRNA expression in PBMCs from three pairs of samples from PMOP patients and controls was initially detected by circRNA microarray. The changes in selected circRNAs in PBMCs from 28 PMOP patients and 21 age- and sex-matched controls were confirmed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Next, samples from 30 PMOP patients and 20 controls were used for further verification. Pearson correlation test was performed to assess the correlation between circRNAs and clinical variables. The area under the receiver operator characteristic (ROC) curve was calculated to evaluate the diagnostic value. Results: Six differentially expressed circRNAs were identified by chip microarray analysis, of which only hsa_circ_0001275 showed consistency and statistical significance in qRT-PCR. The correlation analysis between age, body weight, height, WBC, lymphocyte and monocyte count, bone density, T-score, β-CROSSL, OSTEOC, and TP1NP showed that hsa_circ_0001275 was negatively correlated with T-score. ROC curves showed that hsa_circ_0001275 has significant diagnostic value in PMOP (AUC=0.759, P< 0.001). Conclusion: This study suggests that hsa_circ_0001275 may serve as a potential diagnostic biomarker for PMOP.

The main diagnostic indicators of ovarian cancer (OC), including carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4), show good sensitivity and poor specificity or vice versa. This study investigated changes in CA125 and HE4 expression and their correlation in serum-derived exosomes of 55 patients with OC (OC group), 33 patients with malignant tumors (non-OC group), and 55 normal controls (NC group). We compared serum and exosomal CA125 and HE4 levels to determine whether their contents in exosomes were elevated. We also compared the diagnostic efficacy of serum HE4, serum CA125, exosomal CA125, and serum HE4+exosomal CA125 in OC using the receiver operating characteristic (ROC) curve. CA125 levels in serum-derived exosomes in all groups significantly increased (P < 0.0001) compared with serum CA125 levels. HE4 was undetected in exosomes. The ROC curve showed the following values:

Circular RNAs (circRNAs) are emerging as important regulators in bone metabolism, which is mediated by microRNA (miRNA) sponges. However, it is not clear how circRNA regulates osteogenic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs).Therefore, based on the previous circRNA chip results, hsa_circ_0006766, which is differentially expressed in the osteogenic differentiation of hBM-MSCs, was screened out, and bioinformatics analysis was performed to predict potential target miRNAs. During osteogenic differentiation of hBM-MSCs, hsa_circ_0006766 and its target miRNAs (miR-4739, miR-619-5p, miR-5787, miR-7851-3p, and miR-3192-5p) were detected by quantitative Real Time-PCR (qRT-PCR). Target gene prediction for the differentially expressed target miRNAs was performed, and target genes were validated by dualluciferase reporter gene assay and qRT-PCR. It is shown that hsa_circ_0006766 was up-regulated and miR-4739 was down-regulated during osteogenic differentiation of hBM-MSCs.Moreover, the target gene Notch2 was predicted to be highly expressed during osteogenic differentiation. And dual-luciferase assay proved that Notch2 was the gene targeting to miR-4739. Taken together, our finding confirmed that hsa_-circ_0006766 may act as a major regulatory part in osteogenic differentiation of hBM-MSCs via an hsa_circ_0006766-miR-4739-Notch2 regulatory axis. Accordingly, hsa_circ_0006766 may affect the development of osteoporosis and may thus become a therapeutic target.

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