Soma Lari1, Sarah Hiyari1, Davi Neto de Araújo Silva1,2, Beatriz de Brito Bezerra1, Makiko Ishii3, Sepehr Monajemzadeh1, Zhong-Kai Cui4, Sotirios Tetradis5, Min Lee6, Flavia Q Pirih7. 1. School of Dentistry, Section of Periodontics, University of California, Los Angeles, Los Angeles, Los Angeles, CA, USA. 2. Dentistry Department, Rio Grande do Norte Federal University, Natal, RN, Brazil. 3. Division of Periodontology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, Urayasu, Japan. 4. Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. 5. School of Dentistry, Section of Oral Radiology, University of California, Los Angeles, Los Angeles, CA, USA. 6. School of Dentistry, Section of Biomaterials Science, University of California, Los Angeles, Los Angeles, CA, USA. 7. School of Dentistry, Section of Periodontics, University of California, Los Angeles, Los Angeles, Los Angeles, CA, USA. fpirih@dentistry.ucla.edu.
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.
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.
Authors: Panos N Papapanou; Mariano Sanz; Nurcan Buduneli; Thomas Dietrich; Magda Feres; Daniel H Fine; Thomas F Flemmig; Raul Garcia; William V Giannobile; Filippo Graziani; Henry Greenwell; David Herrera; Richard T Kao; Moritz Kebschull; Denis F Kinane; Keith L Kirkwood; Thomas Kocher; Kenneth S Kornman; Purnima S Kumar; Bruno G Loos; Eli Machtei; Huanxin Meng; Andrea Mombelli; Ian Needleman; Steven Offenbacher; Gregory J Seymour; Ricardo Teles; Maurizio S Tonetti Journal: J Periodontol Date: 2018-06 Impact factor: 6.993
Authors: Søren Jepsen; Jack G Caton; Jasim M Albandar; Nabil F Bissada; Philippe Bouchard; Pierpaolo Cortellini; Korkud Demirel; Massimo de Sanctis; Carlo Ercoli; Jingyuan Fan; Nicolaas C Geurs; Francis J Hughes; Lijian Jin; Alpdogan Kantarci; Evanthia Lalla; Phoebus N Madianos; Debora Matthews; Michael K McGuire; Michael P Mills; Philip M Preshaw; Mark A Reynolds; Anton Sculean; Cristiano Susin; Nicola X West; Kazuhisa Yamazaki Journal: J Periodontol Date: 2018-06 Impact factor: 6.993