牙槽骨是上下颌骨包绕牙根的突起部分,在牙发育、萌出和行使咀嚼功能等过程中发挥重要作用.在根尖周炎、牙周炎和种植体周围炎等口腔炎症性疾病中,牙槽骨缺损造成牙松动脱落和咀嚼功能障碍,危害患者身心健康.然而,由于口腔微环境中复杂的生物、机械和化学等因素综合作用,临床牙槽骨修复重建面临巨大挑战.深入了解牙槽骨修复重建分子调控机制,有助于探寻牙槽骨修复重建新靶点.新近研究表明,Notch、Wnt、Toll样受体(Toll-like receptor,TLR)和核因子-κB(nuclear factor-κB,NF-κB)等信号通路调控破骨细胞、成骨细胞、骨细胞、牙周韧带细胞、巨噬细胞和适应性免疫细胞等增殖、分化、凋亡和自噬等生命活动,调节炎症介质表达,影响核因子-κB受体活化因子配体(receptor activator for nuclear factor-κB ligand,RANKL)/核因子-κB受体活化因子(receptor activator for nuclear factor-κB,RANK)/护骨素(osteoprotegerin,OPG)系统平衡,参与牙槽骨修复重建.此外,牙槽骨修复重建也涉及腺苷酸激活蛋白激酶(AMP-activated protein kinase,AMPK)、磷脂酰肌醇3-激酶(phosphatidyl inositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)、Hippo/YAP、Janus 激酶(Janus kinase,JAK)/转录激活因子(signal transducer and activator of transcription,STAT)和转化生长因子-β(transforming growth factor β,TGF-β)等信号通路.然而,现有研究未能构建出成熟的牙槽骨修复重建分子调控网络,亟需利用单细胞转录组测序和空间转录组测序等新技术进一步加强对牙槽骨修复重建分子调控机制的探索.
Research Progress in the Molecular Regulatory Mechanisms of Alveolar Bone Restoration
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 β(TGF-β)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.
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维普
