Bone Abstracts

Growing body of evidence shows that microRNAs play an important role in regulating bone mass. We investigated the cooperative microRNA-mRNA regulatory mechanism of peak bone mass in inbred strain of mice with different bone density using microarray analysis. Femur and tibia of 12-week old C3H/He (high bone density) and C57BL/6 (low bone density) were harvested to extract total bone RNAs for microarray. A total of 30 miRNAs were differentially expressed between bone tissue of CeH/He and C57BL/6 mice; 16 miRNAs (miR-34c, 101a, 128, 135a, 181b, 181d, 210, 290, 296, 340, 425, 467e, 542, 582, 652, 705) were identified to be upregulated in C3H/He mice, while 11 miRNA (miR-26b, 29c, 34a, 101b, 204, 214, 219, 338, 342, 720, 801) were upregulated in C57BL/6 mice. Concomitant analysis of mRNA microarray revealed that 1189 genes were differentially expressed between C3H/He and C57BL/6 mice. Functional clustering analysis revealed that mRNA of the genes related with the composition of extracellular matrix, microtubule, gap junction and mRNAs of Wnt and TGF-β signaling pathways were upregulated in C3H/He mice. In contrast, the mRNA of genes involved in immune and inflammatory response as well as lipid synthesis were upregulated in C57BL/6 mice. Using the integrative analysis based on computational target prediction of differentially expressed miRNAs and concomitant mRNA profiling, we found that about 20% of differentially expressed mRNAs were putative target of differentially expressed miRNAs. The candidates for miRNA/mRNA regulatory pairs include those of the component of extracellular matrix, microtubule and gap junction, indicating that peak bone mass determination in different strains of mice is at least in part mediated by differential expression of miRNA profile. The miRNA/mRNA expression profiles reported in this study form a comprehensive transcriptome database and provide a valuable resource for understanding the role of miRNA in determining bone mass.