ZOL Reduces Autophagy In Inflammatory Osteoclasts By Down-Regulating Nlrp3

Inflammatory bone resorption is a prominent risk factor for implantation failure. Zoledronic acid (ZOL) is a widely used medication for effectively inhibiting excessive bone destruction, but its effect on alleviating inflammatory bone loss remains to be elucidated. In this study, we investigated whether ZOL alleviates inflammatory bone resorption by immunomodulatory effects. Constructing inflammatory cellular and animal models. The phenotype M1 macrophage polarization of RAW264.7 cells was detected by Flow cytometry (FC). Osteoclast (OC) differentiation and formation were evaluated by tartrate-resistant acid phosphatase (TRAP) staining and F-actin ring staining. The autophagosomes by transmission electron microscopy (TEM). The mRNA expression of osteoclast-related molecules and the protein expression of autophagy-related proteins, and NLRP3 signaling pathway factors in pre-OCs were evaluated by reverse transcription-quantitative PCR (RT‒qPCR) and Western blot (WB) analysis. The OC and microstructure of alveolar bone tissue in C57BL/6J mice were observed using TRAP staining and micro computed tomography (Miro-CT). The results showed that ZOL inhibited LPS-induced OC differentiation, formation and the level of autophagosomes. Furthermore, ZOL attenuated OC-related gene expression, and significantly suppressed LC3II and Beclin1 while upregulating P62 by downregulating NLRP3-related protein expression. ZOL has a certain immunomodulatory effect that exhibits anti-inflammatory properties at lower concentrations, which can alleviates inflammatory bone resorption, and NLRP3-mediated autophagy pathway may participate in this process.