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

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Abstract

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.

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Funding

This work was supported by NIH/NIDCR DE023901-01 and the UCLA Faculty Development grant.

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Authors and Affiliations

  1. School of Dentistry, Section of Periodontics, University of California, Los Angeles, Los Angeles, Los Angeles, CA, USA

    Soma Lari, Sarah Hiyari, Davi Neto de Araújo Silva, Beatriz de Brito Bezerra, Sepehr Monajemzadeh & Flavia Q. Pirih

  2. Dentistry Department, Rio Grande do Norte Federal University, Natal, RN, Brazil

    Davi Neto de Araújo Silva

  3. Division of Periodontology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, Urayasu, Japan

    Makiko Ishii

  4. Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China

    Zhong-Kai Cui

  5. School of Dentistry, Section of Oral Radiology, University of California, Los Angeles, Los Angeles, CA, USA

    Sotirios Tetradis

  6. School of Dentistry, Section of Biomaterials Science, University of California, Los Angeles, Los Angeles, CA, USA

    Min Lee

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  1. Soma Lari
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  2. Sarah Hiyari
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  9. Min Lee
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  10. Flavia Q. Pirih
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Correspondence to Flavia Q. Pirih.

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Lari, S., Hiyari, S., de Araújo Silva, D.N. et al. Local delivery of a CXCR3 antagonist decreases the progression of bone resorption induced by LPS injection in a murine model. Clin Oral Invest 26, 5163–5169 (2022). https://doi.org/10.1007/s00784-022-04484-z

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  • DOI: https://doi.org/10.1007/s00784-022-04484-z

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