John Burton

Introduction. Osteoporosis is a major concern worldwide and can be attributed to a metabolic imbalance between osteoblastic bone formation and osteoclastic bone resorption that increases bone fragility and fracture risk¹. More than 75 million people are currently living with osteoporosis and many more have osteopenia². There are many drugs such as selective estrogen receptor modulators, bisphosphonates, denosumab, teriparatide that we currently use to attenuate the progression of osteoporosis, but they are associated with severe side effects and cannot reverse existing bone loss³. With advancements in gene therapy on the horizon, many experiments have led to the identification of miRNAs that when overexpressed, promote osteogenic differentiation of Human Mesenchymal Stem Cells (hMSCs). Methods. Out of the 818 non-coding RNAs that were dysregulated in osteoporotic patients, miRNAs such as miRNA-130a, miRNA-27b, miRNA-27a-3p, miRNA-19a-3p, and miRNA-483-3p were identified as targets with possible therapeutic properties through bioinformatics, overexpressed in hMSCs, then analyzed through tests such as alizarin red staining and ALP staining to see if they promoted osteogenesis as well as dual-luciferase reporter gene assay to determine what pathway they worked through^4,5,6,7,8. Results. It was found that miR-130a and miR-27b work through RUNX2 (runt-related transcription factor 2) and Osterix promotion, miRNA-27a-3p works through ATF3 (Activating transcription factor 3) inhibition, miRNA-19a-3p works through HDAC4 (Human Deacetylase 4) inhibition and miR-483-3p works through DKK2 (Dickkopf WNT Signaling Pathway Inhibitor 2) suppression to promote osteodifferentiation in hMSCs^4,5,6,7. Conclusions. Although MSC differentiation by gene therapy is difficult as transfection with existing approaches is clinically impractical (viral transfection) or have low efficacy (lipid‐mediated transfection), we now know that the therapeutic overexpression of these miRNAs does not only halt the progression of osteoporosis but can help to reverse existing bone loss through osteodifferentiation of hMSCs⁹. Further advances in gene therapy and being able to overexpress the miRNAs listed in this study would be a revolutionary breakthrough in the treatment of such a widespread and debilitating disease

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