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.
Highlights
Osteoporosis (OP) is a systemic bone disorder characterized by an imbalance between bone formation and resorption, which leads to a reduction in bone mass [1]
18 participants were in control group who had a normal bone mass and16 participants were in severe osteoporosis group (SOP) group who suffered from vertebral fracture (68.75%) and/or hip fracture (43.75%)
Clinical and basic research is constantly progressing, patients are still facing delayed diagnosis and fragility fractures, which indicate that exploration of circulating biomarkers is needed to provide a convenient and noninvasive diagnosis
Summary
Osteoporosis (OP) is a systemic bone disorder characterized by an imbalance between bone formation and resorption, which leads to a reduction in bone mass [1]. Postmenopausal osteoporosis (PMOP) is characterized by low bone mass and consequent fragility fractures, which have impaired quality of life and increased mortality in the population [2, 3]. The miRNA Profiling in Postmenopausal Osteoporosis measurement of BMD by dual energy X-ray absorptiometry (DXA) has been regarded as the “gold standard” and current approaches for predicting fractures are largely based on the measurement of BMD, BMD is associated with only 30–50% patients with major fragility fractures [4]. MiRNAs have attracted extensive attention for their roles in many biological processes, such as cell proliferation, differentiation, apoptosis and migration [6–9]. It is known that miRNAs in serum may be associated with biological processes and play an important role in the progression of diseases. The complexity and inherent heterogeneity of miRNAs in the circulation make it difficult to develop biomarkers and let alone evaluate the prognosis of diseases
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