Yang Xiao, Yixin Li, Shuo Chen, Shiyang Feng, Mengnan Cao, Chenchen Gao, Kai-Yuan Fu, Jie Lei
{"title":"Gli1+成骨祖细胞中YAP缺乏通过β-Catenin信号传导导致髁突发育不全。","authors":"Yang Xiao, Yixin Li, Shuo Chen, Shiyang Feng, Mengnan Cao, Chenchen Gao, Kai-Yuan Fu, Jie Lei","doi":"10.1111/odi.70006","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>The pathogenesis of mandibular condylar hypoplasia has not been fully understood. Our previous studies provided evidence that Gli1<sup>+</sup> osteogenic progenitors contribute to condylar development. This study aimed to investigate the role of YAP in Gli1<sup>+</sup> cells during condylar development.</p><p><strong>Methods: </strong>We generated Gli1-Cre<sup>ERT2</sup>;Yap<sup>fl/fl</sup> mice, in which tamoxifen (TMX) was used to induce the deletion of Yap in Gli1<sup>+</sup> cells. CHIR injection was to activate β-catenin signaling. Microscopic photography, Micro-CT, hematoxylin-eosin (H&E) staining, immunofluorescence (IF) staining, Real-time quantitative polymerase chain reaction (RT-qPCR), tartrate-resistant acid phosphatase (TRAP) staining and calcein-alizarin red double labeling were conducted for analyses. Chromatin immunoprecipitation (ChIP) assay was used to investigate the molecular mechanism involved.</p><p><strong>Results: </strong>YAP co-localized with mandibular condylar Gli1<sup>+</sup> osteogenic progenitors. After induction, Gli1-Cre<sup>ERT2</sup>;Yap<sup>fl/fl</sup> mice suffered from condylar hypoplasia characterized by reduced bone mass and impaired osteogenesis due to decreased cell proliferation. ChIP-qPCR analysis, RT-qPCR analysis, and immunofluorescence staining further proved that YAP could directly regulate the expression of β-catenin. Functionally, pharmacological activation of β-catenin signaling successfully alleviated condylar hypoplasia in Gli1-Cre<sup>ERT2</sup>;Yap<sup>fl/fl</sup> mice.</p><p><strong>Conclusions: </strong>Our study demonstrated that the YAP/β-catenin axis mediated osteogenesis in Gli1<sup>+</sup> osteogenic progenitors during condylar development, which may provide a potential target for the treatment of condylar hypoplasia.</p>","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"YAP Deficiency in Gli1<sup>+</sup> Osteogenic Progenitors Leads to Condylar Hypoplasia via β-Catenin Signaling.\",\"authors\":\"Yang Xiao, Yixin Li, Shuo Chen, Shiyang Feng, Mengnan Cao, Chenchen Gao, Kai-Yuan Fu, Jie Lei\",\"doi\":\"10.1111/odi.70006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>The pathogenesis of mandibular condylar hypoplasia has not been fully understood. Our previous studies provided evidence that Gli1<sup>+</sup> osteogenic progenitors contribute to condylar development. This study aimed to investigate the role of YAP in Gli1<sup>+</sup> cells during condylar development.</p><p><strong>Methods: </strong>We generated Gli1-Cre<sup>ERT2</sup>;Yap<sup>fl/fl</sup> mice, in which tamoxifen (TMX) was used to induce the deletion of Yap in Gli1<sup>+</sup> cells. CHIR injection was to activate β-catenin signaling. Microscopic photography, Micro-CT, hematoxylin-eosin (H&E) staining, immunofluorescence (IF) staining, Real-time quantitative polymerase chain reaction (RT-qPCR), tartrate-resistant acid phosphatase (TRAP) staining and calcein-alizarin red double labeling were conducted for analyses. Chromatin immunoprecipitation (ChIP) assay was used to investigate the molecular mechanism involved.</p><p><strong>Results: </strong>YAP co-localized with mandibular condylar Gli1<sup>+</sup> osteogenic progenitors. After induction, Gli1-Cre<sup>ERT2</sup>;Yap<sup>fl/fl</sup> mice suffered from condylar hypoplasia characterized by reduced bone mass and impaired osteogenesis due to decreased cell proliferation. ChIP-qPCR analysis, RT-qPCR analysis, and immunofluorescence staining further proved that YAP could directly regulate the expression of β-catenin. Functionally, pharmacological activation of β-catenin signaling successfully alleviated condylar hypoplasia in Gli1-Cre<sup>ERT2</sup>;Yap<sup>fl/fl</sup> mice.</p><p><strong>Conclusions: </strong>Our study demonstrated that the YAP/β-catenin axis mediated osteogenesis in Gli1<sup>+</sup> osteogenic progenitors during condylar development, which may provide a potential target for the treatment of condylar hypoplasia.</p>\",\"PeriodicalId\":19615,\"journal\":{\"name\":\"Oral diseases\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-06-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oral diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/odi.70006\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oral diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/odi.70006","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
YAP Deficiency in Gli1+ Osteogenic Progenitors Leads to Condylar Hypoplasia via β-Catenin Signaling.
Objectives: The pathogenesis of mandibular condylar hypoplasia has not been fully understood. Our previous studies provided evidence that Gli1+ osteogenic progenitors contribute to condylar development. This study aimed to investigate the role of YAP in Gli1+ cells during condylar development.
Methods: We generated Gli1-CreERT2;Yapfl/fl mice, in which tamoxifen (TMX) was used to induce the deletion of Yap in Gli1+ cells. CHIR injection was to activate β-catenin signaling. Microscopic photography, Micro-CT, hematoxylin-eosin (H&E) staining, immunofluorescence (IF) staining, Real-time quantitative polymerase chain reaction (RT-qPCR), tartrate-resistant acid phosphatase (TRAP) staining and calcein-alizarin red double labeling were conducted for analyses. Chromatin immunoprecipitation (ChIP) assay was used to investigate the molecular mechanism involved.
Results: YAP co-localized with mandibular condylar Gli1+ osteogenic progenitors. After induction, Gli1-CreERT2;Yapfl/fl mice suffered from condylar hypoplasia characterized by reduced bone mass and impaired osteogenesis due to decreased cell proliferation. ChIP-qPCR analysis, RT-qPCR analysis, and immunofluorescence staining further proved that YAP could directly regulate the expression of β-catenin. Functionally, pharmacological activation of β-catenin signaling successfully alleviated condylar hypoplasia in Gli1-CreERT2;Yapfl/fl mice.
Conclusions: Our study demonstrated that the YAP/β-catenin axis mediated osteogenesis in Gli1+ osteogenic progenitors during condylar development, which may provide a potential target for the treatment of condylar hypoplasia.
期刊介绍：
Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.
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