Abstract
We previously demonstrated the aberrant expression of nine specific miRNAs in serum from osteoporotic patients. In the present study, we further evaluated the expression of these miRNAs in bone tissue, osteoblasts, and osteoclasts from 28 patients. We hypothesize that miRNA expression in serum from osteoporotic patients may be gender-independent. A further hypothesis is that the miRNA expression in bone could be correlated with BMD values. Moreover, intracellular expression of these osteoporosis-related miRNAs may indicate the role of these molecules during osteoporosis. Our results indeed show that miRNA expression in serum was gender-independent except for miR125b-5p. A correlation with BMD was confirmed for miR-21-5p, miR-24-3p, miR-93-5p, miR-100-5p and miR125b-5p with linear correlation coefficients r > 0.9. Intracellular studies revealed a simultaneous up-regulation of miR-21-5p, miR-93-5p, miR-100-5p and miR125b-5p in osteoblasts and in osteoclasts. miR-148a-3p up-regulation in cells was specific for osteoporotic osteoclasts. Altogether, miR-21-5p, miR-93-5p, miR-100-5p, and miR-125b-5p showed significant upregulation in serum, tissue and bone cells of osteoporotic patients. All except miR-125b-5p showed gender independent expression and good correlation to BMD values. Our results suggest that these miRNAs may be important for an earlier diagnosis of osteoporosis.
Highlights
The World Health Organization (WHO) defines osteoporosis as bone mineral density (BMD) values of 2.5 standard deviations below the mean for young white adult women[1]
It must be mentioned that the ability of Dual energy X-ray absorptiometry (DXA) measurements to predict fracture risk remains somewhat controversial
A limitation more associated with therapy screening, is the fact that DXA measurements do not reveal the effect of several treatment drugs
Summary
The World Health Organization (WHO) defines osteoporosis as bone mineral density (BMD) values of 2.5 standard deviations below the mean for young white adult women[1]. DXA-based diagnostics do not consider the contribution of factors like bone microarchitecture, cortical porosity or tissue and cellular level components. MiRNAs are small non-coding RNA segments that regulate many cellular biological functions They can be found circulating in blood, and in diverse tissues and organs and even at cellular levels. The authors elegantly demonstrated that specific in vitro manipulation of miR-214 with an antagomir or mimic in osteoblasts resulted in a clear effect on osteogenesis of these cells They identified ATF4 (activating transcription factor 4) as a target gene of miR-214. The purpose of the present study was to investigate these osteoporosis-associated miRNAs for their correlation with BMD and gender as well as to examine their intracellular expression in bone-specific cells. Our goals were to i) determine the correlation of these miRNAs with clinical values such as BMD and gender and ii) study the intracellular expression of these miRNAs in different bone cell populations
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