1. Local delivery of a CXCR3 antagonist decreases the progression of bone resorption induced by LPS injection in a murine model
- Author
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Lari, Soma, Hiyari, Sarah, de Araújo Silva, Davi Neto, de Brito Bezerra, Beatriz, Ishii, Makiko, Monajemzadeh, Sepehr, Cui, Zhong-Kai, Tetradis, Sotirios, Lee, Min, and Pirih, Flavia Q
- Subjects
Biomedical and Clinical Sciences ,Dentistry ,Bioengineering ,Nanotechnology ,2.1 Biological and endogenous factors ,Aetiology ,Alveolar Bone Loss ,Animals ,Bone Resorption ,Disease Models ,Animal ,Inflammation ,Lipopolysaccharides ,Male ,Mice ,Mice ,Inbred C57BL ,Osteoclasts ,Porphyromonas gingivalis ,AMG-487 nanoparticles ,CXCR3 antagonist ,Bone resorption ,Inflammatory infiltrate ,Osteoclast - Abstract
ObjectivesThis experimental study was carried out to investigate the effects of locally delivered nanoparticles (AMG-487 NP) containing a CXCR3 antagonist in inhibiting the progression of LPS-induced inflammation, osteoclastic activity, and bone resorption on a murine model.Materials and methodsThirty, 7-week-old C57BL/6 J male mice were used. Inflammatory bone loss was induced by Porphyromonas gingivalis-lipopolysaccharide (P.g.-LPS) injections between the first and second maxillary molars, bilaterally, twice a week for 6 weeks (n = 20). AMG-487 NP were incorporated into a liposome carrier and locally delivered on sites where P.g.-LPS was injected. Control mice (n = 10) were injected with vehicle only. Experimental groups included (1) control, (2) LPS, and (3) LPS + NP. At the end of 1 and 6 weeks, mice were euthanized, maxillae harvested, fixed, and stored for further analysis.ResultsVolumetric bone loss analysis revealed, at 1 week, an increase in bone loss in the LPS group (47.9%) compared to control (27.4%) and LPS + NP (27.8%) groups. H&E staining demonstrated reduced inflammatory infiltrate in the LPS + NP group compared to LPS group. At 6 weeks, volumetric bone loss increased in all groups; however, treatment with the CXCR3 antagonist (LPS + NP) significantly reduced bone loss compared to the LPS group. CXCR3 antagonist treatment significantly reduced osteoclast numbers when compared to LPS group at 1 and 6 weeks.ConclusionsThis study showed that local delivery of a CXCR antagonist, via nanoparticles, in a bone resorption model, induced by LPS injection, was effective in reducing inflammation, osteoclast numbers, and bone loss.Clinical relevanceCXCR3 blockade can be regarded as a novel target for therapeutic intervention of bone loss. It can be a safe and convenient method for periodontitis treatment or prevention applicable in clinical practice.
- Published
- 2022