MicroRNAs in Serum Exosomes as Circulating Biomarkers for Postmenopausal Osteoporosis

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.

Impact of Alendronate Sodium plus Elcatonin on Postoperative Bone Pain in Patients with Osteoporotic Fractures

“…OP has a predilection for the elderly and women, and its pathological feature is the disequilibrium between bone formation and bone resorption [ 18 ]. The incidence of OPFs is constantly on the rise, and by 2025, there will be 3 million new OPF patients worldwide, bringing a huge economic burden to the healthcare system [ 19 ].…”

A plasma‐derived exosomal microRNA signature by small RNA sequencing for early detection of postmenopausal osteoporosis

“…Pan Gao 1,2,3 Sijia Li 4 Zhanying Dong 3 Yonglun Luo 3 Xiuqing Zhang 1,3 Linbo Han 4 Songlin Peng 5 Jianliang Shen 6,7,8 Fengping Xu…”

The Potential of Exosomes for Osteoporosis Treatment: A Review

“… 44 A different study examined the variations in circulating miRNAs in serum exosomes among postmenopausal women who had normal bone mass and osteoporotic fractures. 45 The results of the bioinformatics study and sRNA deep sequencing revealed that serum exosomal miRNAs were expressed differently in PMOP patients who had fragility fractures. Bone mineral density (BMD) of L1-L4, femur neck, and total hip was shown to be correlated with three miRNAs (mir-324-3p, mir-766-3p, and mir-1247-5p), whereas BMD of femur neck and total hip was found to be correlated with mir-330-5p and mir-3124-5p.…”