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

STAT3, as a member of signal transducers and activators of transcription (STATs) family,which has been recognized as one of the common pathways in cancer cells. STAT3 has been found in many tumor cells that are critical to cell survival, cell proliferation, invasion, angiogenesis and immune evasion.Thus, STAT3 signaling pathway may be a potential therapeutic target for tumor metastasis.

Objective To investigate the expression of signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (pSTAT3), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in tissues of nonsmall-cell lung cancer (NSCLC) and their relationship. Methods The expression of STAT3, pSTAT3, VEGF and bFGF in tissues of 68 cases of NSCLC and lung tissues of 27 normal cases were detected by immunohistochemistry methods, and their relationship with clinicopathological features was analyzed. Results The expression of STAT3,pSTAT3, VEGF and bFGF in tissues of NSCLC was significantly higher than that in normal lung tissues (P＜0.05). There was positive correlationship among pSTAT3,VEGF and bFGF in tissues of NSCLC (P＜0.05). The expression of STAT3 and pSTAT3 in NSCLC with poor differentiation was higher than that in NSCLC with high or moderate differentiation, the expression in NSCLC at TNM Ⅲ+Ⅳ stage was higher than that in NSCLC at TNMⅠ+Ⅱ stage, and the expression in NSCLC with lymph node metastasis was higher than that in NSCLC without lymph node metastasis(P<0.05). The expression of VEGF and bFGF in NSCLC at TNM Ⅲ+Ⅳ stage was higher than that in NSCLC at TNMⅠ+Ⅱ stage (P<0.05), and the expression of bFGF in NSCLC with lymph node metastasis was higher than that in NSCLC without lymph node metastasis (P<0.05). Conclusion STAT3,pSTAT3,VEGF and bFGF are highly expressed in NSCLC, and are involved in tumor metastasis and invasion.

Objective To investigate the effect of mesenchymal stem cells (MSCs) on subcutaneous xenograft tumors in mice with Lewis lung cancer. Methods MSCs isolated from bone marrow of C57BL/6 mice were made into single cell suspension and were cultured in vitro. The cells of the 4th to 5th passage were used for the subsequent experiments. Fifty six C57BL/6 mice were inoculated subcutaneously with Lewis lung cancer cells, and were grouped into Group D0 (MSCs were given simultaneously with inoculation)and Group D10(MSCs were given 10 d after inoculation). Group D0 included three subgroups (n=8): Group 1 with inoculation of tumor cells, Group 2 with inoculation of tumor cells and MSCs, and Group 3 with inoculation of tumor cells and tail intravenous injection of MSCs. Group D10 included four groups: Group 4 with inoculation of tumor cells and injection of MSCs in tumors, Group 5 with equivalent PBS (the control of Group 4), Group 6 with inoculation of tumor cells and tail intravenous injection of MSCs, and Group 7 with equivalent PBS (the control of Group 6). The time of tumor formation and the volume of tumor were observed and compared among the groups. ResultsIn Group D0, earlier onset of tumor development was observed in Group 2 as compared to Group 1 and Group 3 (P<0.05), while there was no significant difference on the volume of tumor in the three groups (P>0.05). In Group D10, the volume of tumors were larger in Group 4 compared to the control (P<0.05), while there was no significant difference on the volume of tumors between Group 6 and the control (P>0.05). Conclusion Inoculating mixture of MSCs and Lewis lung cancer cells accelerates tumor formation,and injection of MSCs in tumors stimulates the growth of tumors.

Osteopontin (OPN), a phospborylated and glycosylated protein,is a prominent matrices component of the extracellular matrix of mineralized tissues of bones and teeth, in which they can regulate the formation and growth of hydroxyapatite crystals and influence a variety of cell activities.Recent studies have reported that the expression of OPN is not only correlated with bone formation and bone resorption but also with tumor aggression and metastasis in several types of human cancer,and OPN is even considered to be an index for the diagnosis and prognosis of tumor.This article reviews OPN's role in lung cancer' s infiltration, metastasis and prognosis.