{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:35:26Z","timestamp":1791941726942,"version":"4.3.4"},"reference-count":63,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":364,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515010806"],"award-info":[{"award-number":["2021A1515010806"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515010809"],"award-info":[{"award-number":["2022A1515010809"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Peri\u2010implantitis, a major contributor to dental implant failure, lacks comprehensive insights into tissue\u2010specific heterogeneity as current researches predominantly focus on the whole peri\u2010implant tissue rather than distinct molecular and cellular dynamics in gingiva and alveolar bone microenvironments. Furthermore, ethical challenges hinder the acquisition of healthy peri\u2010implant tissues, limiting our understanding of peri\u2010implantitis progression and the development of targeted therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established a controlled peri\u2010implantitis model in beagle dogs, enabling ethical collection of healthy control tissues. Single\u2010cell RNA sequencing (scRNA\u2010seq) transcriptomics profiling was conducted on gingiva and alveolar bone tissues from diseased and healthy controls. Additionally, flow cytometry was utilized to further verify the identified subclusters and their involvement in peri\u2010implantitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Single\u2010cell transcriptomic profiling unveiled a pronounced expansion of inflammation\u2010associated cellular subsets in both gingival and alveolar bone microenvironments during peri\u2010implantitis. Gingival tissues exhibited marked expansions in IL6\n                      <jats:sup>+<\/jats:sup>\n                      \/IL18BP\n                      <jats:sup>+<\/jats:sup>\n                      endothelial cell and CXCL8\n                      <jats:sup>+<\/jats:sup>\n                      fibroblast, whereas APOD\n                      <jats:sup>+<\/jats:sup>\n                      fibroblast dominated in peri\u2010implantitis bone tissues. Gene\u2010level profiling further identified upregulated pro\u2010inflammatory chemokines (\n                      <jats:italic>CXCL8<\/jats:italic>\n                      ,\n                      <jats:italic>CXCL17<\/jats:italic>\n                      ,\n                      <jats:italic>CCL24<\/jats:italic>\n                      ) within gingiva IL18BP\n                      <jats:sup>+<\/jats:sup>\n                      endothelial cells. Notably, we discovered a unique ligand\u2013receptor interaction C3 (APOD\n                      <jats:sup>+<\/jats:sup>\n                      fibroblast)\u2013C3AR1 (monocyte\/macrophage) in alveolar bone tissue, implicating complement\u2010dependent signaling in immune crosstalk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study provides the first comparative atlas of soft\/hard tissue remodeling in peri\u2010implantitis at single\u2010cell resolution. The expansion of IL6\n                      <jats:sup>+<\/jats:sup>\n                      \/IL18BP\n                      <jats:sup>+<\/jats:sup>\n                      endothelial cell and CXCL8\n                      <jats:sup>+<\/jats:sup>\n                      fibroblast in gingiva, alongside APOD\n                      <jats:sup>+<\/jats:sup>\n                      fibroblast\u2010driven C3\u2013C3AR1 signaling in alveolar bone, highlights distinct microenvironmental reprogramming between soft and hard tissues. These findings not only identify potential therapeutic targets but also validate the translational relevance of the canine model for peri\u2010implantitis research.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/mi\/9937505","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:24:23Z","timestamp":1767187463000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Single\u2010Cell Transcriptomics Reveal Microenvironment Alterations in Canine Peri\u2010Implantitis"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0782-688X","authenticated-orcid":false,"given":"Ming","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5051-8860","authenticated-orcid":false,"given":"Dong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6159-4514","authenticated-orcid":false,"given":"Chunhui","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0431-7494","authenticated-orcid":false,"given":"Daner","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5753-4877","authenticated-orcid":false,"given":"Ningbo","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6729-1801","authenticated-orcid":false,"given":"Yixin","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1617-806X","authenticated-orcid":false,"given":"Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5528-2453","authenticated-orcid":false,"given":"Songling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2934-707X","authenticated-orcid":false,"given":"Wei","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1186\/1746-160X-10-34"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034516667484"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12417"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12049"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/clr.13307"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13982"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.05.013"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-020-03435-w"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13912"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom11010085"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000411"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2023.102042"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202250325"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-023-00529-z"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad0501"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/00220345221099442"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2520"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0280634"},{"key":"e_1_2_12_19_2","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2009.0485"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10735-014-9604-1"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-018-0026-7"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-00974-6"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2015.08.263"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2004.apm11207-0808.x"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514559128"},{"key":"e_1_2_12_26_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.15625"},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/9731675"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.1096\/fba.2022-00045"},{"key":"e_1_2_12_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12778"},{"key":"e_1_2_12_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-012-0923-6"},{"key":"e_1_2_12_31_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.227728"},{"key":"e_1_2_12_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1213891"},{"key":"e_1_2_12_33_2","doi-asserted-by":"publisher","DOI":"10.3109\/1354750X.2011.587893"},{"key":"e_1_2_12_34_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0042-1758791"},{"key":"e_1_2_12_35_2","doi-asserted-by":"publisher","DOI":"10.15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