International Journal of Oral Science最新文献_第8页

Mesenchymal stem cell-derived apoptotic bodies alleviate alveolar bone destruction by regulating osteoclast differentiation and function 间充质干细胞衍生的凋亡小体通过调节破骨细胞分化和功能减轻牙槽骨破坏

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2023-12-01 DOI: 10.1038/s41368-023-00255-y

Xiaoyan Li, Yiyang Jiang, Xu Liu, Jingfei Fu, Juan Du, Zhenhua Luo, Junji Xu, Ujjal Kumar Bhawal, Yi Liu, Lijia Guo

{"title":"Mesenchymal stem cell-derived apoptotic bodies alleviate alveolar bone destruction by regulating osteoclast differentiation and function","authors":"Xiaoyan Li, Yiyang Jiang, Xu Liu, Jingfei Fu, Juan Du, Zhenhua Luo, Junji Xu, Ujjal Kumar Bhawal, Yi Liu, Lijia Guo","doi":"10.1038/s41368-023-00255-y","DOIUrl":"https://doi.org/10.1038/s41368-023-00255-y","url":null,"abstract":"Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells (MSCs) are essential for periodontal regeneration. However, the hypoxic periodontal microenvironment during periodontitis induces the apoptosis of MSCs. Apoptotic bodies (ABs) are the major product of apoptotic cells and have been attracting increased attention as potential mediators for periodontitis treatment, thus we investigated the effects of ABs derived from MSCs on periodontitis. MSCs were derived from bone marrows of mice and were cultured under hypoxic conditions for 72 h, after which ABs were isolated from the culture supernatant using a multi-filtration system. The results demonstrate that ABs derived from MSCs inhibited osteoclast differentiation and alveolar bone resorption. miRNA array analysis showed that miR-223-3p is highly enriched in those ABs and is critical for their therapeutic effects. Targetscan and luciferase activity results confirmed that Itgb1 is targeted by miR-223-3p, which interferes with the function of osteoclasts. Additionally, DC-STAMP is a key regulator that mediates membrane infusion. ABs and pre-osteoclasts expressed high levels of DC-STAMP on their membranes, which mediates the engulfment of ABs by pre-osteoclasts. ABs with knock-down of DC-STAMP failed to be engulfed by pre-osteoclasts. Collectively, MSC-derived ABs are targeted to be engulfed by pre-osteoclasts via DC-STAMP, which rescued alveolar bone loss by transferring miR-223-3p to osteoclasts, which in turn led to the attenuation of their differentiation and bone resorption. These results suggest that MSC-derived ABs are promising therapeutic agents for the treatment of periodontitis.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"119 47","pages":""},"PeriodicalIF":14.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138468963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular mechanisms of cellular metabolic homeostasis in stem cells. 干细胞细胞代谢稳态的分子机制。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2023-12-01 DOI: 10.1038/s41368-023-00262-z

Xiaoyu Li, Ou Jiang, Songlin Wang

引用次数: 0

Spatiotemporal cellular dynamics and molecular regulation of tooth root ontogeny. 牙根发生的时空细胞动力学与分子调控。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2023-11-24 DOI: 10.1038/s41368-023-00258-9

Pengcheng Rao, Junjun Jing, Yi Fan, Chenchen Zhou

{"title":"Spatiotemporal cellular dynamics and molecular regulation of tooth root ontogeny.","authors":"Pengcheng Rao, Junjun Jing, Yi Fan, Chenchen Zhou","doi":"10.1038/s41368-023-00258-9","DOIUrl":"10.1038/s41368-023-00258-9","url":null,"abstract":"Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation. The initiation of Hertwig's epithelial root sheath (HERS) induces odontoblast differentiation and the subsequent radicular dentin deposition. Precisely controlled signaling pathways modulate the behaviors of HERS and the fates of dental mesenchymal stem cells (DMSCs). Disruptions in these pathways lead to defects in root development, such as shortened roots and furcation abnormalities. Advances in dental stem cells, biomaterials, and bioprinting show immense promise for bioengineered tooth root regeneration. However, replicating the developmental intricacies of odontogenesis has not been resolved in clinical treatment and remains a major challenge in this field. Ongoing research focusing on the mechanisms of root development, advanced biomaterials, and manufacturing techniques will enable next-generation biological root regeneration that restores the physiological structure and function of the tooth root. This review summarizes recent discoveries in the underlying mechanisms governing root ontogeny and discusses some recent key findings in developing of new biologically based dental therapies.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"15 1","pages":"50"},"PeriodicalIF":14.9,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138434008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Titanium particles in peri-implantitis: distribution, pathogenesis and prospects 钛颗粒在种植体周围炎中的分布、发病机制及前景

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2023-11-23 DOI: 10.1038/s41368-023-00256-x

Long Chen, Zian Tong, Hongke Luo, Yuan Qu, Xinhua Gu, Misi Si

{"title":"Titanium particles in peri-implantitis: distribution, pathogenesis and prospects","authors":"Long Chen, Zian Tong, Hongke Luo, Yuan Qu, Xinhua Gu, Misi Si","doi":"10.1038/s41368-023-00256-x","DOIUrl":"https://doi.org/10.1038/s41368-023-00256-x","url":null,"abstract":"Peri-implantitis is one of the most important biological complications in the field of oral implantology. Identifying the causative factors of peri-implant inflammation and osteolysis is crucial for the disease’s prevention and treatment. The underlying risk factors and detailed pathogenesis of peri-implantitis remain to be elucidated. Titanium-based implants as the most widely used implant inevitably release titanium particles into the surrounding tissue. Notably, the concentration of titanium particles increases significantly at peri-implantitis sites, suggesting titanium particles as a potential risk factor for the condition. Previous studies have indicated that titanium particles can induce peripheral osteolysis and foster the development of aseptic osteoarthritis in orthopedic joint replacement. However, it remains unconfirmed whether this phenomenon also triggers inflammation and bone resorption in peri-implant tissues. This review summarizes the distribution of titanium particles around the implant, the potential roles in peri-implantitis and the prevalent prevention strategies, which expects to provide new directions for the study of the pathogenesis and treatment of peri-implantitis.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"11 5","pages":""},"PeriodicalIF":14.9,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138297488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1. MLL1通过与WDR5相互作用和抑制HES1来抑制SCAPs的神经源性潜能。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2023-10-18 DOI: 10.1038/s41368-023-00253-0

Chen Zhang, Weilong Ye, Mengyao Zhao, Lujue Long, Dengsheng Xia, Zhipeng Fan

{"title":"MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1.","authors":"Chen Zhang, Weilong Ye, Mengyao Zhao, Lujue Long, Dengsheng Xia, Zhipeng Fan","doi":"10.1038/s41368-023-00253-0","DOIUrl":"10.1038/s41368-023-00253-0","url":null,"abstract":"Mesenchymal stem cell (MSC)-based therapy has emerged as a promising treatment for spinal cord injury (SCI), but improving the neurogenic potential of MSCs remains a challenge. Mixed lineage leukemia 1 (MLL1), an H3K4me3 methyltransferases, plays a critical role in regulating lineage-specific gene expression and influences neurogenesis. In this study, we investigated the role and mechanism of MLL1 in the neurogenesis of stem cells from apical papilla (SCAPs). We examined the expression of neural markers, and the nerve repair and regeneration ability of SCAPs using dynamic changes in neuron-like cells, immunofluorescence staining, and a SCI model. We employed a coimmunoprecipitation (Co-IP) assay, real-time RT-PCR, microarray analysis, and chromatin immunoprecipitation (ChIP) assay to investigate the molecular mechanism. The results showed that MLL1 knock-down increased the expression of neural markers, including neurogenic differentiation factor (NeuroD), neural cell adhesion molecule (NCAM), tyrosine hydroxylase (TH), βIII-tubulin and Nestin, and promoted neuron-like cell formation in SCAPs. In vivo, a transplantation experiment showed that depletion of MLL 1 in SCAPs can restore motor function in a rat SCI model. MLL1 can combine with WD repeat domain 5 (WDR5) and WDR5 inhibit the expression of neural markers in SCAPs. MLL1 regulates Hairy and enhancer of split 1 (HES1) expression by directly binds to HES1 promoters via regulating H3K4me3 methylation by interacting with WDR5. Additionally, HES1 enhances the expression of neural markers in SCAPs. Our findings demonstrate that MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1. These results provide a potential therapeutic target for promoting the recovery of motor function in SCI patients.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"15 1","pages":"48"},"PeriodicalIF":14.9,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49677340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sclerostin antibody improves alveolar bone quality in the Hyp mouse model of X-linked hypophosphatemia (XLH). 在X连锁低磷血症（XLH）的Hyp小鼠模型中，硬化蛋白抗体可改善牙槽骨质量。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2023-10-10 DOI: 10.1038/s41368-023-00252-1

Kelsey A Carpenter, Delia O Alkhatib, Bryan A Dulion, Elizabeth Guirado, Shreya Patel, Yinghua Chen, Anne George, Ryan D Ross

{"title":"Sclerostin antibody improves alveolar bone quality in the Hyp mouse model of X-linked hypophosphatemia (XLH).","authors":"Kelsey A Carpenter, Delia O Alkhatib, Bryan A Dulion, Elizabeth Guirado, Shreya Patel, Yinghua Chen, Anne George, Ryan D Ross","doi":"10.1038/s41368-023-00252-1","DOIUrl":"10.1038/s41368-023-00252-1","url":null,"abstract":"X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads to hypophosphatemia and impaired mineralization of bone and teeth. The clinical manifestations of XLH include a high prevalence of dental abscesses and periodontal disease, likely driven by poorly formed structures of the dentoalveolar complex, including the alveolar bone, cementum, dentin, and periodontal ligament. Our previous studies have demonstrated that sclerostin antibody (Scl-Ab) treatment improves phosphate homeostasis, and increases long bone mass, strength, and mineralization in the Hyp mouse model of XLH. In the current study, we investigated whether Scl-Ab impacts the dentoalveolar structures of Hyp mice. Male and female wild-type and Hyp littermates were injected with 25 mg·kg-1 of vehicle or Scl-Ab twice weekly beginning at 12 weeks of age and euthanized at 20 weeks of age. Scl-Ab increased alveolar bone mass in both male and female mice and alveolar tissue mineral density in the male mice. The positive effects of Scl-Ab were consistent with an increase in the fraction of active (nonphosphorylated) β-catenin, dentin matrix protein 1 (DMP1) and osteopontin stained alveolar osteocytes. Scl-Ab had no effect on the mass and mineralization of dentin, enamel, acellular or cellular cementum. There was a nonsignificant trend toward increased periodontal ligament (PDL) attachment fraction within the Hyp mice. Additional PDL fiber structural parameters were not affected by Scl-Ab. The current study demonstrates that Scl-Ab can improve alveolar bone in adult Hyp mice.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"15 1","pages":"47"},"PeriodicalIF":14.9,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41182497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Double heterozygous pathogenic mutations in KIF3C and ZNF513 cause hereditary gingival fibromatosis. KIF3C和ZNF513的双重杂合致病突变可引起遗传性牙龈纤维瘤病。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2023-09-26 DOI: 10.1038/s41368-023-00244-1

Jianfan Chen, Xueqing Xu, Song Chen, Ting Lu, Yingchun Zheng, Zhongzhi Gan, Zongrui Shen, Shunfei Ma, Duocai Wang, Leyi Su, Fei He, Xuan Shang, Huiyong Xu, Dong Chen, Leitao Zhang, Fu Xiong

{"title":"Double heterozygous pathogenic mutations in KIF3C and ZNF513 cause hereditary gingival fibromatosis.","authors":"Jianfan Chen, Xueqing Xu, Song Chen, Ting Lu, Yingchun Zheng, Zhongzhi Gan, Zongrui Shen, Shunfei Ma, Duocai Wang, Leyi Su, Fei He, Xuan Shang, Huiyong Xu, Dong Chen, Leitao Zhang, Fu Xiong","doi":"10.1038/s41368-023-00244-1","DOIUrl":"10.1038/s41368-023-00244-1","url":null,"abstract":"Hereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST, inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.C748T, p.R250W) and KIF3C (c.G1229A, p.R410H) genes within the GINGF3 locus related to HGF. Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo. ZNF513, a transcription factor, binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts. Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. In addition, we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1. Moreover, the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels. ZNF513 combined with KIF3C regulates gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways. In summary, these results demonstrate ZNF513 + KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"15 1","pages":"46"},"PeriodicalIF":14.9,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10522663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41130359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptional profiling of dental sensory and proprioceptive trigeminal neurons using single-cell RNA sequencing. 使用单细胞RNA测序的牙齿感觉和本体感觉三叉神经神经元的转录谱。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2023-09-25 DOI: 10.1038/s41368-023-00246-z

Pa Reum Lee, Jihoon Kim, Heather Lynn Rossi, Sena Chung, Seung Yub Han, Junhyong Kim, Seog Bae Oh

{"title":"Transcriptional profiling of dental sensory and proprioceptive trigeminal neurons using single-cell RNA sequencing.","authors":"Pa Reum Lee, Jihoon Kim, Heather Lynn Rossi, Sena Chung, Seung Yub Han, Junhyong Kim, Seog Bae Oh","doi":"10.1038/s41368-023-00246-z","DOIUrl":"10.1038/s41368-023-00246-z","url":null,"abstract":"Dental primary afferent (DPA) neurons and proprioceptive mesencephalic trigeminal nucleus (MTN) neurons, located in the trigeminal ganglion and the brainstem, respectively, are essential for controlling masticatory functions. Despite extensive transcriptomic studies on various somatosensory neurons, there is still a lack of knowledge about the molecular identities of these populations due to technical challenges in their circuit-validated isolation. Here, we employed high-depth single-cell RNA sequencing (scRNA-seq) in combination with retrograde tracing in mice to identify intrinsic transcriptional features of DPA and MTN neurons. Our transcriptome analysis revealed five major types of DPA neurons with cell type-specific gene enrichment, some of which exhibit unique mechano-nociceptive properties capable of transmitting nociception in response to innocuous mechanical stimuli in the teeth. Furthermore, we discovered cellular heterogeneity within MTN neurons that potentially contribute to their responsiveness to mechanical stretch in the masseter muscle spindles. Additionally, DPA and MTN neurons represented sensory compartments with distinct molecular profiles characterized by various ion channels, receptors, neuropeptides, and mechanoreceptors. Together, our study provides new biological insights regarding the highly specialized mechanosensory functions of DPA and MTN neurons in pain and proprioception.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"15 1","pages":"45"},"PeriodicalIF":14.9,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41125789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oral squamous cell carcinomas: state of the field and emerging directions. 口腔鳞状细胞癌：研究现状和发展方向。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2023-09-22 DOI: 10.1038/s41368-023-00249-w

Yunhan Tan, Zhihan Wang, Mengtong Xu, Bowen Li, Zhao Huang, Siyuan Qin, Edouard C Nice, Jing Tang, Canhua Huang

{"title":"Oral squamous cell carcinomas: state of the field and emerging directions.","authors":"Yunhan Tan, Zhihan Wang, Mengtong Xu, Bowen Li, Zhao Huang, Siyuan Qin, Edouard C Nice, Jing Tang, Canhua Huang","doi":"10.1038/s41368-023-00249-w","DOIUrl":"10.1038/s41368-023-00249-w","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% of oral malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. In 2020, 377,713 OSCC cases were reported globally. According to the Global Cancer Observatory (GCO), the incidence of OSCC will rise by approximately 40% by 2040, accompanied by a growth in mortality. Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ), and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oral mucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involves genetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. Although various therapeutic interventions, such as chemotherapy, radiation, immunotherapy, and nanomedicine, have been proposed to prevent or treat OSCC and OPMDs, understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors, thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC. Moreover, the current therapeutic interventions and prognostic methods for OSCC and OPMDs are discussed to facilitate comprehension and provide several prospective outlooks for the fields.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"15 1","pages":"44"},"PeriodicalIF":14.9,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41125788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Porphyromonas gingivalis, a periodontal pathogen, impairs post-infarcted myocardium by inhibiting autophagosome-lysosome fusion. 牙龈卟啉单胞菌是一种牙周病原体，通过抑制自噬体-溶酶体融合来损害梗死后的心肌。

IF 14.9 1区医学

International Journal of Oral Science Pub Date : 2023-09-18 DOI: 10.1038/s41368-023-00251-2

Yuka Shiheido-Watanabe, Yasuhiro Maejima, Shun Nakagama, Qintao Fan, Natsuko Tamura, Tetsuo Sasano

{"title":"Porphyromonas gingivalis, a periodontal pathogen, impairs post-infarcted myocardium by inhibiting autophagosome-lysosome fusion.","authors":"Yuka Shiheido-Watanabe, Yasuhiro Maejima, Shun Nakagama, Qintao Fan, Natsuko Tamura, Tetsuo Sasano","doi":"10.1038/s41368-023-00251-2","DOIUrl":"10.1038/s41368-023-00251-2","url":null,"abstract":"While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), the underlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, including heart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment by periodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate the relationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes (NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagy inhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. This study also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomal sensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity than gingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wild-type P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-type P.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which are virulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms the strong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.","PeriodicalId":14191,"journal":{"name":"International Journal of Oral Science","volume":"15 1","pages":"42"},"PeriodicalIF":14.9,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10507114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10674050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0