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Emerging evidence indicates that many microRNAs (miRNAs) are indispensable regulators of osteoblast differentiation and bone formation. However, the role of miRNAs in mechanotransduction of osteoblasts remains to be elucidated. This study aimed to identify a mechanosensitive miRNA that regulates Activin A receptor type I (ACVR1)-induced osteogenic differentiation. After 4 weeks of hindlimb unloading (HLU) suspension of 6-month-old male C57BL/6J mice, femurs and tibias were harvested to extract total bone RNAs. Elevated levels of miR-208a-3p correlated with a lower degree of bone formation in whole-bone samples of HLU mice. However, in vitro overexpression of miR-208a-3p inhibited osteoblast differentiation, whereas silencing of miR-208a-3p by antagomiR-208a-3p promoted expression of osteoblast activity, bone formation marker genes, and matrix mineralization under mechanical unloading condition. Bioinformatics analysis and a luciferase assay revealed that ACVR1 is a target gene of miR-208a-3p that negatively regulates osteoblast differentiation under mechanical unloading environment. Further, this study also demonstrates that in vivo pre-treatment with antagomiR-208a-3p led to an increase in bone formation and trabecular microarchitecture and partly rescued the bone loss caused by mechanical unloading. Collectively, these results suggest that in vivo, inhibition of miRNA-208a-3p by antagomiR-208a-3p may be a potential therapeutic strategy for ameliorating bone loss.

Abstract:Background: In view of the increasing popularity of complementary and alternative medicine (CAM), it is imperative that medical students, the health professionals of tomorrow, possess adequate knowledge on the topic. Objectives: This is a descriptive study designed to assess the knowledge, attitudes and behavior of medical students about CAM and to capture their perceptions and opinions about its integration into the medical curriculum. Methods: A questionnaire-based cross-sectional survey was done on 198 medical students selected randomly from a Pakistani medical college. Associations between different variables were tested using the χ2-test of significance. Results: Among the 198 participants, a majority believed that some of the CAM modalities are useful; they lacked knowledge, however, about their safety and efficacy. Most of the students believed that it should be used in conjunction with conventional medicine and that, if given adequate training, they would incorporate it in their future medical practice. One-third of the respondents voted in favor of incorporation of CAM into the medical curriculum. Conclusion: Despite being aware of the usefulness of CAM only a few medical students had pursued further knowledge. In order to prepare the medical students of today to better fulfill their duties as tomorrow's physicians, consideration should be given to incorporating CAM in the medical curriculum.

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