Altered Microrna Expression Profile in the peripheral Lymphomonocytes of Multiple Myeloma Patients with Bisphosphonate-Induced Osteonecrosis of the Jaw

Background: Bisphosphonates are formidable inhibitors of osteoclast-mediated bone resorption employed for therapy of multiple myeloma (MM) subjects with osteolytic lesions. Osteonecrosis of the jaw (ONJ) is an uncommon drug-induced adverse event of these agents. MicroRNAs (miRNAs) are a group of small, noncoding RNAs nucleotides, which are essential post-transcriptional controllers of gene expression. They have a central role in the normal bone development. Aims: The goal of our study was to investigate 18 miRNAs, whose targets were previously validated and described in MM subjects without ONJ, in peripheral lymphomonocytes of MM subjects with bisphosphonate-induced ONJ. Methods: Utilizing reverse transcription quantitative polymerase chain reaction we evaluated miRNAs in five healthy subjects and in five MM patients with ONJ. Results: Our experimental data revealed that a diverse miRNA signature for ONJ subjects emerged respect to control subjects. Using the filter for in silico analysis, among 18 miRNAs we recognized 14 dysregulated miRNAs. All of these miRNAs were significantly over). Among them, six were strongly up-regulated (4-fold up-regulated and more). These miRNAs target numerous pathways and genes implicated in calcium ion binding, bone resorption, mineralization of bone matrix, differentiation and maintenance of bone tissue. Summary/Conclusion: A modified microRNA expression profile after zoledronate therapy could participate to the onset of ONJ. Targeting these miRNAs could provide a new treatment for the prevention or treatment of ONJ.