{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T18:38:25Z","timestamp":1757702305634,"version":"3.40.5"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T00:00:00Z","timestamp":1586736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100011002","name":"National Natural Science Foundation of China-Yunnan Joint Fund","doi-asserted-by":"publisher","award":["No. 81600836"],"award-info":[{"award-number":["No. 81600836"]}],"id":[{"id":"10.13039\/501100011002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To analyze the heterogeneity of fibroblasts isolated from the fibrous capsules of radicular cysts and explore the effects of fibroblast subsets on bone destruction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>Radicular cysts were divided into groups according to varying perilesional sclerosis identified by radiograph. Colony\u2010forming units (CFUs) were isolated from the fibrous capsules of cysts, by which Trap\u00a0+\u00a0MNCs were induced, and the expression of osteoclastogenesis\u2010related genes was compared among groups by real\u2010time PCR. The variances in gene profiles of CFUs were identified by principal component analysis, and then, CFUs were divided into subsets using cluster analysis. The induction of Trap\u00a0+\u00a0MNCs and related gene expression was compared among subsets, and osteoclastogenic induction was blocked by IST\u20109 or bevacizumab. The fibroblast subsets in cysts were investigated by retrospective immunostaining with IST\u20109, VEGF\u2010A, and CD34. A fibroblast subset that underwent gene editing by CRISPR\/Cas was injected into the site of bone defects in animal models, and the in vivo effects on osteoclastogenesis were investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The fibroblast CFUs isolated from radicular cysts with perilesional unsclerotized cysts induced more Trap\u00a0+\u00a0MNCs than those with perilesional sclerotic cysts (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05). Most fibroblast CFUs from unsclerotized cysts belonged to Cluster 2, which induced more Trap\u00a0+\u00a0MNCs (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05) and highly expressed genes facilitating osteoclastogenesis; these results were different from those of Cluster 1 (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05), in which most CFUs were isolated from perilesional sclerotic cysts or controls (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05). The high expression of EDA\u00a0+\u00a0FN and VEGF\u2010A was investigated in both the fibroblasts of Cluster 2 and the fibrous capsules of unsclerotized cysts (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05), and the number of Trap\u00a0+\u00a0MNCs induced by Cluster 2 was decreased by treatment with IST\u20109 and bevacizumab (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05). Consistently, EDA exon exclusion significantly decreased the osteoclastogenic induction of fibroblasts from Cluster 2 in vivo (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The fibrous capsules of radicular cysts contain heterogeneous fibroblasts that can form subsets exhibiting different effects on osteoclastogenesis. The subset, which depending on the autocrine effects of EDA\u00a0+\u00a0FN on VEGF\u2010A, mainly contributes to the osteoclastogenesis and bone destruction of radicular cysts. The regulation of the proportion of subsets is a possible strategy for artificially interfering with osteoclastogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/odi.13317","type":"journal-article","created":{"date-parts":[[2020,2,29]],"date-time":"2020-02-29T14:32:36Z","timestamp":1582986756000},"page":"983-997","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Heterogeneity of fibroblasts from radicular cyst influenced osteoclastogenesis and bone destruction"],"prefix":"10.1111","volume":"26","author":[{"given":"Jingwen","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Prosthodontics Peking University School and Hospital of Stomatology Beijing China"},{"name":"National Engineering Laboratory for Digital and Material Technology of Stomatology Beijing China"},{"name":"Research Center of Engineering and Technology for Digital Dentistry of Ministry of Health Beijing China"},{"name":"Beijing Key Laboratory of Digital Stomatology Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuyu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oral Implant School &amp; Hospital Stomatology Shanghai Engineering Research Center of Tooth Restoration and Regeneration Tongji University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8189-6424","authenticated-orcid":false,"given":"Hai\u2010Cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology School &amp; Hospital of Stomatology Shanghai Engineering Research Center of Tooth Restoration and Regeneration Tongji University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2015.08.036"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.12.051"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0642-7"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature.2016.20988"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2011.05.009"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12783"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-016-0418-9"},{"issue":"8","key":"e_1_2_8_9_1","first-page":"E585","article-title":"The post\u2010endodontic periapical lesion: Histologic and etiopathogenic aspects","volume":"12","author":"Garcia C. 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