{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T13:17:45Z","timestamp":1788182265673,"version":"build-2803163510"},"reference-count":32,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"the Academician Laboratory of Immune and Oral Development & Regeneration, Dalian Medical University","award":["2021002"],"award-info":[{"award-number":["2021002"]}]},{"name":"the Shandong Natural Science Foundation","award":["ZR2024MH061"],"award-info":[{"award-number":["ZR2024MH061"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82470951"],"award-info":[{"award-number":["82470951"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"abstract":"<jats:p>\n                    Macrophages are increasingly recognized as key regulators of organogenesis, yet their contributions to tooth germ development remain poorly understood. Here, we integrated analysis of publicly available single-cell RNA sequencing datasets with multiplex immunohistochemistry to investigate the presence, distribution, and activation states of macrophages during tooth development. Macrophages were enriched in the dental follicle and dental papilla, expanded through local proliferation, and displayed a predominant tissue-resident macrophage (TRM)\u2013like and M2-like phenotype. Spatial and transcriptomic analyses further revealed that macrophages preferentially localized adjacent to developing blood vessels and established a localized provascular niche enriched for vascular regulatory signaling pathways. Functional depletion of macrophages, both in vivo using\n                    <jats:italic toggle=\"yes\">Cx3cr1<\/jats:italic>\n                    -dependent DTA mice and ex vivo with clodronate liposomes, impaired tooth germ growth and morphogenetic progression, accompanied by reduced tooth germ size, abnormal cusp morphology, increased apoptosis, and impaired vascular maturation. Notably, macrophage depletion reduced vascular maturation without markedly affecting overall vascular density. Given the well-established requirement for vascular maturation in tooth development and the close spatial association between macrophages and developing vessels, we examined whether macrophages contribute to the immune-vascular interactions required for morphogenesis. Macrophages expressed multiple vascular regulatory factors, including VEGFA, TGF-\u03b2, and IL1B, while inhibition of vascular maturation phenocopied the developmental abnormalities caused by macrophage depletion and was associated with attenuated bone morphogenetic protein\u2013associated signaling. Together, these findings identify macrophages as important upstream regulators of tooth germ morphogenesis, acting in part by modulating vascular maturation, and provide new insights into immune-vascular crosstalk during tooth development.\n                  <\/jats:p>","DOI":"10.1177\/00220345261470395","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:16:26Z","timestamp":1787890586000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophages Promote Vascular Maturation to Support Tooth Germ Morphogenesis"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9729-9736","authenticated-orcid":false,"given":"Z.","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8942-1850","authenticated-orcid":false,"given":"M.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7066-2654","authenticated-orcid":false,"given":"R.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Laboratory of Oral Health, School of Basic Medical Sciences, Capital Medical University, Beijing, China"},{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology &amp; National Center of Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Obstetrics and Gynecology Hospital, Capital Medical University\/Beijing Maternal and Child Health Care Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Obstetrics and Gynecology Hospital, Capital Medical University\/Beijing Maternal and Child Health Care Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7435-2637","authenticated-orcid":false,"given":"S.","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Laboratory of Oral Health, School of Basic Medical Sciences, Capital Medical University, Beijing, China"},{"name":"Laboratory of Homeostatic Medicine, School of Medicine and SUSTech Homeostatic Medicine Institute, Southern University of Science and Technology, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7636-8974","authenticated-orcid":false,"given":"F.","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University &amp; Shandong Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration &amp; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"crossref","unstructured":"Alghadeer A et al. 2023. 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