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Nanoparticulate cell-free DNA scavenger for treating inflammatory bone loss in periodontitis

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机构: [1]State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. [2]Department of Biomedical Engineering, Columbia University, New York 10027 NY, USA. [3]Department of Oral Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. [4]Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China [5]Advanced Biomaterials and Tissue Engineering Center and Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China. [6]Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, the Republic of Korea. [7]Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, China. [8]Department of Orthopaedic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Guangzhou, Guangdong 510000, China. [9]Department of Orthodontics and Pediatric Dentistry, School of Dentistry, The University of Michigan, Ann Arbor 48109 MI, USA. [10]Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. [11]Department of Systems Biology, Columbia University Medical Center, New York 10032 NY, USA. [12]Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, Zhejiang 310016, China. [13]School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
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Periodontitis is a common type of inflammatory bone loss and a risk factor for systemic diseases. The pathogenesis of periodontitis involves inflammatory dysregulation, which represents a target for new therapeutic strategies to treat periodontitis. After establishing the correlation of cell-free DNA (cfDNA) level with periodontitis in patient samples, we test the hypothesis that the cfDNA-scavenging approach will benefit periodontitis treatment. We create a nanoparticulate cfDNA scavenger specific for periodontitis by coating selenium-doped hydroxyapatite nanoparticles (SeHANs) with cationic polyamidoamine dendrimers (PAMAM-G3), namely G3@SeHANs, and compare the activities of G3@SeHANs with those of soluble PAMAM-G3 polymer. Both G3@SeHANs and PAMAM-G3 inhibit periodontitis-related proinflammation in vitro by scavenging cfDNA and alleviate inflammatory bone loss in a mouse model of ligature-induced periodontitis. G3@SeHANs also regulate the mononuclear phagocyte system in a periodontitis environment, promoting the M2 over the M1 macrophage phenotype. G3@SeHANs show greater therapeutic effects than PAMAM-G3 in reducing proinflammation and alveolar bone loss in vivo. Our findings demonstrate the importance of cfDNA in periodontitis and the potential for using hydroxyapatite-based nanoparticulate cfDNA scavengers to ameliorate periodontitis.© 2022. The Author(s).

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Q1 MULTIDISCIPLINARY SCIENCES
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第一作者机构: [1]State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. [2]Department of Biomedical Engineering, Columbia University, New York 10027 NY, USA. [3]Department of Oral Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
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通讯机构: [1]State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. [2]Department of Biomedical Engineering, Columbia University, New York 10027 NY, USA. [10]Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. [11]Department of Systems Biology, Columbia University Medical Center, New York 10032 NY, USA.
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