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

作者：Lari, Soma; Hiyari, Sarah; de Araujo Silva, Davi Neto; Bezerra, Beatriz de Brito; Ishii, Makiko; Monajemzadeh, Sepehr; Cui, Zhong-Kai; Tetradis, Sotirios; Lee, Min; Pirih, Flavia Q.^*

来源：Clinical Oral Investigations, 2022, 26(8): 5163-5169.

DOI：10.1007/s00784-022-04484-z

• AMG-487 nanoparticles
• CXCR3 antagonist
• Bone resorption
• Inflammatory infiltrate
• Osteoclast

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.

• 单位
  南方医科大学