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MicroRNAs in Serum Exosomes as Circulating Biomarkers for Postmenopausal Osteoporosis
Hongli Shi1, Xin Jiang1, Cuidi Xu1
1Department of Osteoporosis and Bone Disease, Huadong Hospital Affiliated to Fudan University, Research Section of Geriatric Metabolic Bone Disease, Shanghai Geriatric Institute, Shanghai, China.
Abstract:
Postmenopausal osteoporosis (PMOP) is the most common skeletal disease in postmenopausal women and has become a global public health issue. Emerging evidence demonstrated the important relationship between microRNAs and PMOP. However, miRNAs have not yet been reported in PMOP. Hence, the present study aimed to investigate the differences in miRNA expression profiles in PMOP with fragility fractures to identify the key circulating miRNAs in serum exosomes and to validate these molecules as potential biomarkers. Postmenopausal women with osteoporotic fracture and normal bone mass were enrolled. Serum exosomes were isolated by traditional differential ultracentrifugation from participants. Isolated exosomes were identified by electron microscopy, western blotting and nanoparticle-tracking analysis and then examined for exosomal small RNA sequencing. The expression of miRNAs was compared by sRNA deep sequencing and bioinformatics analysis. Three miRNAs (mir-324-3p, mir-766-3p and mir-1247-5p) were found to be associated with BMD of L1-L4, FN (femur neck) and TH (total hip), while mir-330-5p and mir-3124-5p were associated with BMD of FN and TH. Furthermore, mir-330-5p was found to promote the ALP activity of hBMSCs, while mir-3124-5p showed the opposite result. The results showed that serum exosomal miRNAs were differentially expressed in postmenopausal osteoporosis patients with fragility fractures. Our study provides the first evidence that exosomal miRNA profiling revealed aberrant circulating miRNA in postmenopausal osteoporosis. Mir-324-3p, mir-766-3p, mir-1247-5p, mir-330-5p and mir-3124-5p, which were associated with bone mineral density (BMD), may serve as candidate diagnostic biomarkers as well as potentially contribute to pathophysiology of PMOP.
Insights
This study identifies specific microRNAs (miRNAs) in serum exosomes that are linked to postmenopausal osteoporosis (PMOP) and bone mineral density (BMD). These miRNAs show potential as diagnostic biomarkers for PMOP.
Area of Science:
- Endocrinology
- Genetics
- Biochemistry
Background:
- Postmenopausal osteoporosis (PMOP) is a prevalent skeletal disorder in women, with a significant global health impact.
- MicroRNAs (miRNAs) are increasingly recognized for their role in various diseases, but their specific involvement in PMOP remains underexplored.
Purpose of the Study:
- To investigate differential miRNA expression profiles in postmenopausal women with osteoporosis and fragility fractures.
- To identify circulating miRNAs within serum exosomes as potential biomarkers for PMOP.
- To explore the functional role of specific miRNAs in bone metabolism.
Main Methods:
- Serum exosomes were isolated from postmenopausal women with osteoporotic fractures and healthy controls using differential ultracentrifugation.
- Exosome characterization involved electron microscopy, western blotting, and nanoparticle-tracking analysis.
- Small RNA sequencing and bioinformatics analysis were employed to compare miRNA expression profiles and associate them with bone mineral density (BMD) measurements.
Main Results:
- Five specific miRNAs (mir-324-3p, mir-766-3p, mir-1247-5p, mir-330-5p, and mir-3124-5p) were found to be differentially expressed and associated with BMD at various skeletal sites.
- mir-330-5p was observed to promote alkaline phosphatase (ALP) activity in human bone marrow-derived stem cells (hBMSCs), while mir-3124-5p exhibited an inhibitory effect.
- This study presents the first evidence of aberrant circulating exosomal miRNA profiles in postmenopausal osteoporosis patients.
Conclusions:
- Circulating exosomal miRNAs are differentially expressed in postmenopausal women with osteoporosis and fragility fractures.
- The identified miRNAs (mir-324-3p, mir-766-3p, mir-1247-5p, mir-330-5p, mir-3124-5p) are potential candidate biomarkers for diagnosing PMOP.
- These miRNAs may also play a role in the pathophysiology of postmenopausal osteoporosis.
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