Local delivery of a CXCR3 antagonist decreases the progression of bone resorption induced by LPS injection in a murine model

• Published in: Clinical oral investigations 2022-08, Vol.26 (8), p.5163-5169
• Main Authors: Lari, Soma, Hiyari, Sarah, de Araújo Silva, Davi Neto, de Brito Bezerra, Beatriz, Ishii, Makiko, Monajemzadeh, Sepehr, Cui, Zhong-Kai, Tetradis, Sotirios, Lee, Min, Pirih, Flavia Q.
• Format: Article
• Language: English
• Subjects: Alveolar Bone Loss - drug therapy; Alveolar Bone Loss - prevention & control; Animal models; Animals; Bone loss; Bone resorption; Bone Resorption - drug therapy; Bone Resorption - prevention & control; CXCR3 protein; Dentistry; Disease Models, Animal; Inflammation; Injection; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Male; Medicine; Mice; Mice, Inbred C57BL; Molars; Nanoparticles; Original Article; Osteoclasts; Periodontitis; Porphyromonas gingivalis
• ISSN: 1436-3771; 1432-6981; 1436-3771
• DOI: 10.1007/s00784-022-04484-z

Objectives This 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 methods Thirty, 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. Results Volumetric 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. Conclusions This 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 relevance CXCR3 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.