Liu Jianing, He Junxi, Zhang Ziqi, Liu Lu, Cao Yuan, Zhang Xiaohui, Cai Xinyue, Luo Xinyan, Lei Xiao, Zhang Nan, Wang Hao, Chen Ji, Liu Peisheng, Tian Jiongyi, Liu Jiexi, Gao Yuru, Xu Haokun, Ma Chao, Bai Shengfeng, Zhang Yubohan, Jin Yan, Zheng Chenxi, Sui Bingdong, Jin Fang
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
Int J Oral Sci. 2025 Jul 24;17(1):56. doi: 10.1038/s41368-025-00384-6.
Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA dental follicle stem cells (DFSCs) and CD31 Endomucin endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
牙周骨缺损主要由牙周炎引起，在临床环境中非常普遍，表现为骨开窗、骨裂开或附着丧失，对口腔健康构成重大挑战。在再生医学中，利用发育原理进行组织修复具有广阔的治疗潜力。特别值得关注的是祖细胞的凝聚，这是器官发生中的一个关键事件，启发了牙科再生中临床上有效的细胞聚集方法。然而，凝聚和再生过程中精确的细胞协调机制仍然不清楚。在这里，以牙齿作为模型器官，我们采用单细胞RNA测序来剖析人牙囊和牙乳头的细胞组成和异质性，揭示了具有显著牙源性潜力的独特的血小板衍生生长因子受体α（PDGFRA）间充质干/基质细胞（MSC）群体。有趣的是，PDGFRA牙囊干细胞（DFSCs）和CD31内黏液素内皮细胞（ECs）之间的相互旁分泌相互作用由血管内皮生长因子A（VEGFA）和血小板衍生生长因子亚基BB（PDGFBB）介导。这种串扰不仅维持了PDGFRA DFSCs的功能，还驱动了特殊的血管生成。体内牙周骨再生实验进一步表明，PDGFRA DFSC聚集体与受体ECs之间的通讯对于有效的血管生成-成骨偶联和快速组织修复至关重要。总的来说，我们的结果揭示了由VEGFA和PDGFBB-PDGFRA相互信号介导的MSC-EC串扰在协调血管生成和成骨中的重要性。这些发现不仅为潜在临床应用中解读和促进牙周骨再生建立了一个框架，也为牙科或更广泛的再生医学中的未来治疗策略提供了见解。
