Zoledronic Acid Inhibits Lipopolysaccharide-Induced Osteoclastogenesis by Suppressing Macrophage NLRP3-Mediated Autophagy Pathway.

Publisher: John Wiley and Sons Ltd Country of Publication: England NLM ID: 101635460 Publication Model: Print Cited Medium: Internet ISSN: 2050-4527 (Electronic) Linking ISSN: 20504527 NLM ISO Abbreviation: Immun Inflamm Dis Subsets: MEDLINE

Original Publication: [Oxford] : John Wiley and Sons Ltd, [2013]-

Zoledronic Acid*/pharmacology ; Autophagy*/drug effects ; Lipopolysaccharides*/toxicity ; NLR Family, Pyrin Domain-Containing 3 Protein*/metabolism ; Osteoclasts*/drug effects ; Osteoclasts*/metabolism ; Osteogenesis*/drug effects ; Macrophages*/metabolism ; Macrophages*/drug effects; Animals ; Mice ; Cell Differentiation/drug effects ; Mice, Inbred C57BL ; Signal Transduction/drug effects ; Bone Resorption/metabolism ; Bone Resorption/pathology ; Bone Resorption/drug therapy ; RAW 264.7 Cells

Introduction: Inflammatory factors leading to bone loss significantly increase the risk of tooth loosening or 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 through immunomodulatory effect.
Methods: The viability of the cells was evaluated by Cell Counting Kit 8 (CCK8) assay. Osteoclast (OC) differentiation and function were determined by tartrate-resistant acid phosphatase (TRAP) staining and bone resorption pits assays, respectively. Autophagosomes and actin ring structures of OC were observed using transmission electron microscopy (TEM) and F-actin ring staining, respectively. The microstructure in mice maxillary alveolar bone model was observed by micro computed tomography (Miro-CT). Reverse transcription-quantitative PCR (RT-qPCR) to detect the mRNA expression of osteoclast-related genes and Western blot (WB) analysis to evaluate the protein expression levels of autophagy-related proteins and the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3)-related proteins in pre-OCs.
Results: The findings indicated that ZOL hindered lipopolysaccharide (LPS)-mediated OC differentiation, formation, bone resorption activity and autophagosome levels. Furthermore, ZOL diminished the expression of genes associated with OC. And the expression of proteins ATG7, LC3II, Beclin1, NLRP3-related proteins and tumor necrosis factor-α (TNF-α) protein were markedly decreased while P62 was increased, especially in the 1 μM ZOL group or MCC950 + ZOL group.
Conclusions: ZOL has a certain immunomodulatory effect that exhibits anti-inflammatory properties at lower concentrations, which can weaken LPS-induced OCs differentiation and function, and NLRP3-mediated autophagy pathway may participate in this process.
(© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

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The present study was supported by the Natural Science Foundation of China (grant nos. 82260198 and 82060207), the Science and Technology Foundation of Guizhou Provincial Health Commission (grant no. gzwkj2023-437) and the Foundation of School/Hospital of Stomatology of Guizhou Medical University (grant no. GYKQKY2022-03).

Keywords: NLRP3; autophagy; bone resorption; lipopolysaccharide; osteoclast; zoledronic acid

6XC1PAD3KF (Zoledronic Acid)
0 (Lipopolysaccharides)
0 (NLR Family, Pyrin Domain-Containing 3 Protein)
0 (Nlrp3 protein, mouse)

Date Created: 20241216 Date Completed: 20241216 Latest Revision: 20241216

20241216

10.1002/iid3.70094

39679857