Circulating miR-181c-5p and miR-497-5p Are Potential Biomarkers for Prognosis and Diagnosis of Osteoporosis

Abstract

Context Osteoporosis is a degenerative bone disease in aging men and women. MiRNAs associated with progressive bone loss in osteoporosis had not been clearly demonstrated. Objective The evaluation of the differentially expressed miRNAs in the bone tissue and serum of osteoporotic women with aging. Methods MiRNAs GeneChip and real-time PCR were used to screen differently expressed miRNAs in bone tissues of 21 osteoporotic women ages 60–69 years and 80–89 years. Identified miRNAs were detected in the serum of the validation cohort, which consisted of 14 healthy premenopausal women and 86 postmenopausal women with osteopenia or osteoporosis. MiR-181c-5p and miR-497-5p expression were validated in aging and OVX mice models, and osteoblasts. Their role in osteogenesis was validated in vitro. Results Twenty-four miRNAs showed the highest differential expression in bone tissues of osteoporotic women in initial screening. Among them, four miRNAs were identified both in the bone tissue and serum in the validation cohort. The levels of miR-181c-5p and miR-497-5p were decreased in the serum of postmenopausal women with osteopenia or osteoporosis, but increased in subjects treated with bisphosphonate plus calcitriol. MiR-181c-5p and miR-497-5p were significantly downregulated in the bone tissue of aging and OVX mice models, and upregulated during the osteogenic differentiation of hFOB1.19 and MC3T3-E1 cells. Overexpression of miR-181c-5p and miR-497-5p promoted the differentiation and mineralization of osteoblasts. Conclusions MiR-181c-5p and miR-497-5p are involved in bone metabolism and associated with progressive bone loss of due to osteoporosis, suggesting that circulating miR-181c-5p and miR-497-5p might act as potential biomarkers for monitoring the effects of antiosteoporotic therapies or the diagnostic approach.

Circulating MicroRNAs as Novel Biomarkers for Osteoporosis and Fragility Fracture Risk: Is There a Use in Assessment Risk?

“…Moreover, miR-204-3p was positively correlated with BMI and CTx and negatively correlated with BMD, whereas miR-181c-5p and miR-497-5p results were negatively correlated with the latter parameter. Lastly, ROC analysis and functional studies suggested that all three miRs may be used as biomarkers to distinguish LBMD patients from healthy subjects, and that both miR-181c-5p and miR-497-5p were involved in OB differentiation processes [56].…”

Unique, Gender-Dependent Serum microRNA Profile in PLS3 Gene-Related Osteoporosis

“…Three miRNAs-miR-181c-5p, miR-203a-3p, and miR-218-5p-are predicted or experimentally validated to interact with or bind to PLS3. First, miR-181c-5p, which relates to postmenopausal osteoporosis and fracture risk in diabetic patients, (13,15,35) inhibits osteoblast proliferation in simulated microgravity-settings through interactions with cyclin B1. (36) Here, we could experimentally validate the interaction between miR-181c-5p and PLS3.…”

The Clinical Potential of Circulating miRNAs as Biomarkers: Present and Future Applications for Diagnosis and Prognosis of Age-Associated Bone Diseases

“…Women with postmenopausal OP reveal decreased serum levels of miR-33-3p after 3 months and miR-133a after 12 months of teriparatide treatment [83]. In addition, postmenopausal OP and osteopenia women treated with anti-OP therapy revealed more elevated serum levels of miR-497-5p and miR-181c-5p than the OP and osteopenia postmenopausal women without anti-OP therapy, respectively [84].…”