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.

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.

Gap junction (GJ) has been indicated to have an intimate correlation with adhesion junction. However, the direct interaction between them partially remains elusive. In the current study, we aimed to elucidate the role of N-cadherin, one of the core components in adhesion junction, in mediating connexin 43, one of the functional constituents in gap junction, via transforming growth factor-β1(TGF-β1) induction in osteoblasts. We first elucidated the expressions of N-cadherin induced by TGF-β1 and also confirmed the upregulation of Cx43, and the enhancement of functional gap junctional intercellular communication (GJIC) triggered by TGF-β1 in both primary osteoblasts and MC3T3 cell line. Colocalization analysis and Co-IP experimentation showed that N-cadherin interacts with Cx43 at the site of cell-cell contact. Knockdown of N-cadherin by siRNA interference decreased the Cx43 expression and abolished the promoting effect of TGF-β1 on Cx43. Functional GJICs in living primary osteoblasts and MC3T3 cell line were also reduced. TGF-β1-induced increase in N-cadherin and Cx43 was via Smad3 activation, whereas knockdown of Smad3 signaling by using siRNA decreased the expressions of both N-cadherin and Cx43. Overall, these data indicate the direct interactions between N-cadherin and Cx43, and reveal the intervention of adhesion junction in functional gap junction in living osteoblasts.
Cadherins ; Cell Communication ; Connexin 43 ; Osteoblasts ; Transforming Growth Factor beta1

Homoeostasis depends on the close connection and intimate molecular exchange between extracellular, intracellular and intercellular networks. Intercellular communication is largely mediated by gap junctions (GJs), a type of specialized membrane contact composed of variable number of channels that enable direct communication between cells by allowing small molecules to pass directly into the cytoplasm of neighbouring cells. Although considerable evidence indicates that gap junctions contribute to the functions of many organs, such as the bone, intestine, kidney, heart, brain and nerve, less is known about their role in oral development and disease. In this review, the current progress in understanding the background of connexins and the functions of gap junctions in oral development and diseases is discussed. The homoeostasis of tooth and periodontal tissues, normal tooth and maxillofacial development, saliva secretion and the integrity of the oral mucosa depend on the proper function of gap junctions. Knowledge of this pattern of cell-cell communication is required for a better understanding of oral diseases. With the ever-increasing understanding of connexins in oral diseases, therapeutic strategies could be developed to target these membrane channels in various oral diseases and maxillofacial dysplasia.
Bone and Bones ; Cell Communication ; Connexins ; metabolism ; physiology ; Gap Junctions ; metabolism ; pathology ; Homeostasis ; physiology ; Humans ; Mouth Diseases ; Phosphorylation