MicroRNA profiles associated with bone healing of the extraction socket in bisphosphonate related osteonecrosis of the jaw in rat model

Abstract

Bisphoshonates (BPs) are widely used for treating osteoporosis, multiple myeloma, breast cancer, and bone metastasis cancer. Trauma or tooth extraction in patients treated with BPs can lead to MRONJ development because of its mechanism of action by which interferes bone homeostasis and angiogenesis. Once MRONJ has occurred, this hard-to-cure disease posed the risk of having poor quality of life to the patients. The application of miRNA for curing the diseases is now being of interest in medical field. Aiming at elucidating the role of miRNAs in the pathogenesis of MRONJ, a rat model was used in creating MRONJ and the expression of candidate miRNAs was evaluated in this study. Seventeen rats were randomly divided into 2 groups; 1) zolendronate plus dexamethasone-treated group (Zol) and 2) control group which receiving normal saline solution (NSS). Tooth extraction was performed after 2 weeks of BPs administration. The MRONJ occurred in extraction sockets were confirmed by clinical appearances, micro-CT, and histological analysis at Day 28 post-extraction. Bone samples from extraction sites were collected for miRNA analysis. In this study, MRONJ in rat model was successfully established in Zol group. Candidate miRNAs were found to be involving in the development of MRONJ. miRNAs that affected an inhibition of osteoblast maturation, including miR-23a-3p, miR-23b-3p, miR27a-3p and miR-24-3p were upregulated in MRONJ bone tissue samples. Promote-angiogenesis-relating miRNAs such as miR-663a and miR-720 were down regulation in the MRONJ extraction sockets. The expression of miR-34 that had dual effects on both bone remodeling and blood vessel formation was upregulated. This study suggested that the certain miRNAs have a role in controlling the cellular functions related to bone remodeling mechanisms and angiogenic activity in MRONJ.