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Circulating miR-181c-5p and miR-497-5p are potential biomarkers for prognosis and diagnosis of osteoporosis

Ma J1,2,3,4Lin X1,2,3Chen C1,2,3,5Li S1,2,3Zhang S1,2,3Chen Z1,2,3Li D1,2,3Zhao F1,2,3Yang C1,2,3Qiu W1,2,3Xiao Y1,2,3Zhang K1,2,3Miao Z1,2,3Yang T5Qian A1,2,3.

J Clin Endocrinol Metab. 2019 Dec 24. pii: dgz300. doi: 10.1210/clinem/dgz300. [Epub ahead of print]

 

 

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:

Evaluation of the differentially expressed miRNAs in 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 aged osteoporotic women at 60-69 years and 80-89 years. Identified miRNAs were detected in serum of validation cohort consisted of 14 healthy premenopausal women and 86 postmenopausal women with osteopenia or osteoporosis. MiR-181c-5p and miR-497-3p expression were validated in aging and OVX mice models, and osteoblasts. Their role in osteogenesis was validated in vitro.

RESULTS:

24 miRNAs were found to be top differentially expressed in bone tissues of osteoporotic women in initial screening. 4 miRNAs were identified both in bone tissue and serum in the validation cohort. Among them, 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 bone tissue of aging and OVX mice models, and upregulated in osteogenic differentiation of hFOB1.19 and MC3T3-E1 cells. Overexpression of miR-181c-5p and miR-497-5p could promote the differentiation and mineralization of osteoblast.

CONCLUSIONS:

MiR-181c-5p and miR-497-5p are involved in bone metabolism and associated with progressive bone loss of osteoporosis, suggesting that circulating miR-181c-5p and miR-497-5p might act as potential biomarkers for monitoring effects of anti-osteoporosis therapies or diagnostic approach.