J Clin Endocrinol Metab. 2019 Dec 24. pii: dgz300. doi: 10.1210/clinem/dgz300. [Epub ahead of print]
Osteoporosis is a degenerative bone disease in aging men and women. MiRNAs associated with progressive bone loss in osteoporosis had not been clearly demonstrated.
Evaluation of the differentially expressed miRNAs in bone tissue and serum of osteoporotic women with aging.
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.
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.
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.