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Clinical value of hsa_circ_0003254 in postmenopausal osteoporosis and its role in the progression of osteoporosis
Zhen Chen1, Ruiquan Tan2, Yong Dai1
1Department of Orthopaedics, Dongguan Qingxi Hospital, Dongguan City, Guangdong Province, China.
Insights
Elevated hsa_circ_0003254 levels are linked to postmenopausal osteoporosis (PMOP). This circular RNA (circRNA) shows diagnostic potential and may drive osteoporosis progression by affecting osteogenic differentiation.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Circular RNAs (circRNAs) are key regulators in human diseases.
- The specific role of circRNAs in postmenopausal osteoporosis (PMOP) requires further investigation.
Purpose of the Study:
- To investigate the expression pattern of hsa_circ_0003254 in postmenopausal osteoporosis (PMOP).
- To evaluate the diagnostic value of hsa_circ_0003254 for PMOP.
- To explore the biological function of hsa_circ_0003254 in osteogenesis.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) to detect hsa_circ_0003254 expression in 207 postmenopausal females.
- Receiver operating characteristic (ROC) analysis and logistic regression to assess diagnostic value.
- In vitro experiments using human bone marrow-derived stem cells (hBMSCs) to study the functional role of hsa_circ_0003254 in osteogenesis, including Western blot analysis for key osteogenic markers.
Main Results:
- Hsa_circ_0003254 expression was significantly higher in patients with osteopenia (OPn) and osteoporosis (OP) compared to healthy controls.
- Hsa_circ_0003254 demonstrated significant diagnostic efficacy for PMOP (AUC=0.876 for OP vs. Health, AUC=0.934 for OPn vs. OP) and was identified as a risk factor.
- Functional studies indicated that hsa_circ_0003254 negatively regulates osteogenic differentiation, with overexpression suppressing osteogenic markers and knockdown enhancing them.
Conclusions:
- Hsa_circ_0003254 may serve as a potential circulating biomarker for PMOP.
- Elevated hsa_circ_0003254 expression is implicated in the progression of osteoporosis by modulating osteogenic differentiation.
Objective:
Circular RNAs (circRNAs) are important regulators of human disease, yet their specific mechanistic role in postmenopausal osteoporosis (PMOP) remains unclear. This study aimed to investigate the expression pattern, diagnostic value, and biological function of hsa_circ_0003254.
Methods:
This study enrolled 207 postmenopausal females grouped into osteopenia (OPn, n = 72), osteoporosis (OP, n = 85), and healthy controls (Health, n = 50). RT-qPCR was employed to detect expression differences of hsa_circ_0003254, receiver operating characteristic (ROC) analysis, and logistic regression were utilized to assess its diagnostic value. The functional role of hsa_circ_0003254 in osteogenesis was assessed by transfecting hBMSCs with pcDNA-circ or si-circ. Western blot analysis was performed to determine the protein levels of RUNX2, ALP, and OCN.
Results:
Analysis of the clinical cohort revealed that the expression of hsa_circ_0003254 was significantly elevated in patients with OPn and OP compared to healthy controls. Its expression level showed a significant positive correlation with both the PINP and the CTX-1. ROC analysis confirmed the diagnostic efficacy of hsa_circ_0003254 for PMOP, distinguishing healthy controls from OP patients (AUC = 0.876) and differentiating OPn from OP patients (AUC = 0.934). Multivariate logistic regression analysis confirmed hsa_circ_0003254 as a risk factor for PMOP (OR = 18.507, p < 0.001). Functionally, Osteogenic induction downregulated hsa_circ_0003254. Overexpression suppressed ALP activity, cell viability, and osteogenic gene expression (ALP, RUNX2, OCN), while knockdown enhanced all these parameters.
Conclusions:
Hsa_circ_0003254 may serve as a potential circulating biomarker for PMOP. Its elevated expression might participate in osteoporosis progression by regulating osteogenic differentiation.
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