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.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Objective To study the efficacy of low dose of combined angiotensin Ⅱ type 1 receptor blockade(ARB)valsartan with angiotensin-converting enzyme inhibitor(ACEI)ramipril on the expression of the gene of angiotensin Ⅱ type 1 receptor(AT1R)and type 2 receptor(AT2R)in cardiovascular vessels and brain in SHR.Methods SHRs 7-8 weeks old were received valsartan 30 mg/(kg?d),or ramipril 1 mg/(kg?d),or valsartan 15 mg/(kg?d)combined with ramipril 0.5 mg/(kg?d)by gavage for three months.SBP,LV/BW ratio,plasma angiotensin Ⅱ,plasma and myocardial NO levels were determined.The severity of myocardial interstitial fibrosis was assessed by image analysis.ACE mRNA,AT1R mRNA and AT2R mRNA expression were detected in the LV myocardium,aorta and brain by the RT-PCR.Results Combined low dose of valsartan and ramipril was shown to reduce more significantly the expression of AT1R mRNA and ACE mRNA in myocardium,aorta and brain than valsartan or ramipril monotherapy(AT1R mRNA:P