PDGF-AA guides cell crosstalk between human dental pulp stem cells in vitro via the PDGFR-α/PI3K/Akt axis.

AIM: To explore the influence of PDGF-AA on cell communication between human dental pulp stem cells (DPSCs) by characterizing gap junction intercellular communication (GJIC) and its potential biomechanical mechanism. METHODOLOGY: Quantitative real-time PCR was used to measure connexin family member expression in DPSCs. Cell migration and CCK-8 assays were utilized to examine the influence of PDGF-AA on DPSC migration and proliferation. A scrape loading/dye transfer assay was applied to evaluate GJIC triggered by PDGF-AA, a PI3K/Akt signalling pathway blocker (LY294002) and a PDGFR-α blocker (AG1296). Western blotting and immunofluorescence were used to test the expression and distribution of the Cx43 and p-Akt proteins in DPSCs. Scanning electron microscopy (SEM) and immunofluorescence were used to observe the morphology of GJIC in DPSCs. RESULTS: PDGF-AA promoted gap junction formation and intercellular communication between human dental pulp stem cells. PDGF-AA upregulates the expression of Cx43 to enhance gap junction formation and intercellular communication. PDGF-AA binds to PDGFR-α and activates PI3K/Akt signalling to regulate cell communication. CONCLUSIONS: This research demonstrated that PDGF-AA can enhance Cx43-mediated GJIC in DPSCs via the PDGFR-α/PI3K/Akt axis, which provides new cues for dental pulp regeneration from the perspective of intercellular communication.

[Research Progress of Cellular Lipid Droplets in Oral Diseases]. / ç»†èƒžè„‚æ»´åœ¨å£è ”ç–¾ç— ä¸­çš„ç ”ç©¶è¿›å±•.

Lipid droplets are dynamic multifunctional organelles composed of a neutral lipid core and a phospholipid monolayer membrane modified by a specific set of proteins. PAT family proteins are the most characteristic lipid droplet proteins, playing an important role in regulating lipid droplet structure, function, and metabolism. The biogenesis of lipid droplets involves neutral lipid synthesis and the nucleation, budding, and growth of the lipid droplets. Lipid droplets not only serve as the energy metabolism reserve of cells but also participate in intracellular signal transduction and the development of inflammation and tumor. Lipid droplets are closely connected to and interact with various organelles, regulating the division, the transportation, and the genetics of organelles. The complexity of lipid droplets biogenesis and the diversity of their functions may have provided a physiological basis for the pathogenesis and development of diseases, but further research is needed in order to better understand the relevant processes. Published findings have helped elucidate the association between lipid droplets and diseases, such as obesity, non-alcoholic fatty liver disease, neurodegenerative disease, cancer, and cardiovascular disease, but the relationship between lipid droplets and oral diseases has not been fully studied. Topics that warrant further research include the role and mechanisms of lipid droplets in the pathogenesis and development of oral diseases, the relationship between oral diseases and systemic diseases, and translation of the effect of lipid droplets on oral diseases into valuable clinical diagnostic and treatment methods. Herein, we reviewed the biogenesis and functions of lipid droplets and the progress in research concerning lipid droplets in oral diseases, including mouth neoplasms, periodontitis, and dental caries.

[Research Progress in the Molecular Regulatory Mechanisms of Alveolar Bone Restoration]. / ç‰™æ§½éª¨ä¿®å¤é‡å»ºåˆ†å­è°ƒæŽ§æœºåˆ¶çš„ç ”ç©¶æ–°è¿›å±•.

Alveolar bone, the protruding portion of the maxilla and the mandible that surrounds the roots of teeth, plays an important role in tooth development, eruption, and masticatory performance. In oral inflammatory diseases, including apical periodontitis, periodontitis, and peri-implantitis, alveolar bone defects cause the loosening or loss of teeth, impair the masticatory function, and endanger the physical and mental health of patients. However, alveolar bone restoration is confronted with great clinical challenges due to the the complicated effect of the biological, mechanical, and chemical factors in the oral microenvironment. An in-depth understanding of the underlying molecular regulatory mechanisms will contribute to the exploration of new targets for alveolar bone restoration. Recent studies have shown that Notch, Wnt, Toll-like receptor (TLR), and nuclear factor-κB (NF-κB) signaling pathways regulate the proliferation, differentiation, apoptosis, and autophagy of osteoclasts, osteoblasts, osteocytes, periodontal ligament cells, macrophages, and adaptive immune cells, modulate the expression of inflammatory mediators, affect the balance of the receptor activator for nuclear factor-κB ligand/receptor activator for nuclear factor-κB/osteoprotegerin (RANKL/RANK/OPG) system, and ultimately participate in alveolar bone restoration. Additionally, alveolar bone restoration involves AMP-activated protein kinase (AMPK), phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT), Hippo/YAP, Janus kinase/signal transducer and activator of transcription (JAK/STAT), and transforming growth factor ß (TGF-ß) signaling pathways. However, current studies have failed to construct mature molecular regulatory networks for alveolar bone restoration. There is an urgent need for further research on the molecular regulatory mechanisms of alveolar bone restoration by using new technologies such as single-cell transcriptome sequencing and spatial transcriptome sequencing.

TGF-ß2 enhances glycolysis in chondrocytes via TßRI/p-Smad3 signaling pathway.

Chondrocytes rely heavily on glycolysis to maintain the metabolic homeostasis and cartilage matrix turnover. Glycolysis in chondrocytes is remodeled by diverse biochemical and biomechanical factors due to the sporty joint microenvironment. Transforming growth factor-ß2 (TGF-ß2), one of the most abundant TGF-ß superfamily members in chondrocytes, has increasingly attracted attention in cartilage physiology and pathology. Although previous studies have emphasized the importance of TGF-ß superfamily members on cell metabolism, whether and how TGF-ß2 modulates glycolysis in chondrocytes remains elusive. In the current study, we investigated the effects of TGF-ß2 on glycolysis in chondrocytes and explored the underlying biomechanisms. The results showed that TGF-ß2 could enhance glycolysis in chondrocytes by increasing glucose consumption, up-regulating liver-type ATP-dependent 6-phosphofructokinase (Pfkl) expression, and boosting lactate production. The TGF-ß2 signal entered chondrocytes via TGF-ß receptor type I (TßRI), and activated p-Smad3 signaling to regulate the glycolytic pathway. Subsequent experiments employing specific inhibitors of TßRI and p-Smad3 further substantiated the role of TGF-ß2 in enhancement of glycolysis via TßRI/p-Smad3 axis in chondrocytes. The results provide new understanding of the metabolic homeostasis in chondrocytes induced by TGF-ß superfamily and might shed light on the prevention and treatment of related osteoarticular diseases.