Zoledronic Acid's Impact On Mirna Differences In Rat Jaw

The jaw bones of rats treated with bisphosphonates alone showed early necrosis signs. This study aimed to analyze the MicroRNA expression differences in the jaw bones of rats before and after such zoledronic acid-treated, and explore the potential mechanism and biological process of MRONJ. Ethical approval for the study protocol (protocol number:YYS-DWLL-2023502) was obtained. Nine 8-week-old male Sprague-Dawley rats were randomly divided into control group (N), zoledronic acid group (ZA), and zoledronic acid + tooth extraction group (ZA-O). Normal saline was injected intravenously in group N, and zoledronic acid in the other two groups for 12 weeks. In group ZA-O, bilateral maxillary first molars were extracted at the 12th week. HE and MASSON staining evaluated bone tissue changes. MicroRNA-seq screened differentially expressed micrornas, and target gene prediction and enrichment analysis were done. ZA and ZA-O groups exhibited jaw osteonecrosis severity. ZA group showed altered miR-148b-3p, miR-29b-3p, and miR-125a-5p levels versus N group, while miR-206-3p and miR-328a-3p differed versus ZA-O. These miRNAs regulate bone metabolism, enriched in MAPK, Hedgehog, Hippo, and Wnt pathways. The expression pattern of MicroRNA in the jaws is changed after zoledronic acid treatment alone or combined with trauma, and it is closely related to bone metabolism, which may be a key signal to promote the occurrence and development of MRONJ.