PMID- 34826339 OWN - NLM STAT- MEDLINE DCOM- 20220118 LR - 20220118 IS - 1600-0765 (Electronic) IS - 0022-3484 (Linking) VI - 57 IP - 1 DP - 2022 Jan TI - Exosomes from dental pulp cells attenuate bone loss in mouse experimental periodontitis. PG - 162-172 LID - 10.1111/jre.12949 [doi] AB - BACKGROUND AND OBJECTIVE: Exosomes are small vesicles secreted from many cell types. Their biological effects largely depend on their cellular origin and the physiological state of the originating cells. Exosomes secreted by mesenchymal stem cells exert therapeutic effects against multiple diseases and may serve as potential alternatives to stem cell therapies. We previously established and characterized human leukocyte antigen (HLA) haplotype homo (HHH) dental pulp cell (DPC) lines from human wisdom teeth. In this study, we aimed to investigate the effect of local administration of HHH-DPC exosomes in a mouse model of periodontitis. METHODS: Exosomes purified from HHH-DPCs were subjected to particle size analysis, and expression of exosome markers was confirmed by western blotting. We also confirmed the effect of exosomes on the migration of both HHH-DPCs and mouse osteoblastic MC3T3-E1 cells. A mouse experimental periodontitis model was used to evaluate the effect of exosomes in vivo. The morphology of alveolar bone was assessed by micro-computed tomography (muCT) and histological analysis. The effect of exosomes on osteoclastogenesis was evaluated using a co-culture system. RESULTS: The exosomes purified from HHH-DPCs were homogeneous and had a spherical membrane structure. HHH-DPC exosomes promoted the migration of both human DPCs and mouse osteoblastic cells. The MTT assay showed a positive effect on the proliferation of human DPCs, but not on mouse osteoblastic cells. Treatment with HHH-DPC exosomes did not alter the differentiation of osteoblastic cells. Imaging with microCT revealed that the exosomes suppressed alveolar bone resorption in the mouse model of periodontitis. Although no change was apparent in the dominance of TRAP-positive osteoclast-like cells in decalcified tissue sections upon exosome treatment, HHH-DPC exosomes significantly suppressed osteoclast formation in vitro. CONCLUSIONS: HHH-DPC exosomes stimulated the migration of human DPCs and mouse osteoblastic cells and effectively attenuated bone loss due to periodontitis. CI - (c) 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Shimizu, Yuta AU - Shimizu Y AUID- ORCID: 0000-0002-5341-9521 AD - Division of Oral Infections and Health Sciences, Department of Periodontology, Asahi University School of Dentistry, Gifu, Japan. FAU - Takeda-Kawaguchi, Tomoko AU - Takeda-Kawaguchi T AD - Department of Oral Maxillofacial Surgery, Gifu University Graduate School of Medicine, Gifu, Japan. FAU - Kuroda, Izumi AU - Kuroda I AD - Department of Stem Cell and Regenerative Medicine, Gifu University Graduate School of Medicine, Gifu, Japan. FAU - Hotta, Yasuaki AU - Hotta Y AD - Central Research Institute of Oral Science, Asahi University School of Dentistry, Gifu, Japan. FAU - Kawasaki, Hideya AU - Kawasaki H AD - Institute for NanoSuit Research, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Shizuoka, Japan. FAU - Hariyama, Takahiko AU - Hariyama T AD - Institute for NanoSuit Research, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Shizuoka, Japan. FAU - Shibata, Toshiyuki AU - Shibata T AD - Department of Oral Maxillofacial Surgery, Gifu University Graduate School of Medicine, Gifu, Japan. FAU - Akao, Yukihiro AU - Akao Y AD - United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan. FAU - Kunisada, Takahiro AU - Kunisada T AD - Department of Stem Cell and Regenerative Medicine, Gifu University Graduate School of Medicine, Gifu, Japan. FAU - Tatsumi, Junichi AU - Tatsumi J AD - Division of Oral Infections and Health Sciences, Department of Periodontology, Asahi University School of Dentistry, Gifu, Japan. FAU - Tezuka, Ken-Ichi AU - Tezuka KI AD - Department of Stem Cell and Regenerative Medicine, Gifu University Graduate School of Medicine, Gifu, Japan. AD - Center for Highly Advanced Integration of Nano and Life Sciences, Gifu University (G-CHAIN), Gifu, Japan. LA - eng GR - JP17K11830/Japan Society for the Promotion of Science/ GR - JP26293426/Japan Society for the Promotion of Science/ GR - JP19K10263/Japan Society for the Promotion of Science/ GR - JP20K10158/Japan Society for the Promotion of Science/ GR - Ministry of Education, Culture, Sports, Science and Technology of Japan/ PT - Journal Article DEP - 20211126 PL - United States TA - J Periodontal Res JT - Journal of periodontal research JID - 0055107 SB - IM MH - *Alveolar Bone Loss/diagnostic imaging/therapy MH - Animals MH - Cell Differentiation MH - Dental Pulp MH - *Exosomes MH - Mice MH - *Periodontitis/therapy MH - X-Ray Microtomography OTO - NOTNLM OT - dental pulp cells OT - exosomes OT - ligature-induced mouse model OT - periodontal disease EDAT- 2021/11/27 06:00 MHDA- 2022/01/19 06:00 CRDT- 2021/11/26 17:08 PHST- 2021/09/07 00:00 [received] PHST- 2021/10/12 00:00 [accepted] PHST- 2021/11/27 06:00 [pubmed] PHST- 2022/01/19 06:00 [medline] PHST- 2021/11/26 17:08 [entrez] AID - 10.1111/jre.12949 [doi] PST - ppublish SO - J Periodontal Res. 2022 Jan;57(1):162-172. doi: 10.1111/jre.12949. Epub 2021 Nov 26.