Journal of Dental Research最新文献

{"title":"Analysis of Hepatitis D Virus in Minor Salivary Gland of Sjögren's Disease.","authors":"M C Hesterman, S V Furrer, B S Fallon, M L Weller","doi":"10.1177/00220345231186394","DOIUrl":"10.1177/00220345231186394","url":null,"abstract":"<p><p>Hepatitis delta virus (HDV) has been detected in the minor salivary gland (MSG) tissue of Sjögren's disease (SjD) patients in the absence of a hepatitis B virus (HBV) coinfection. Previous research has shown that HDV antigen (HDAg) expression can trigger an SjD-like phenotype in vivo, demonstrating a potential cause-and-effect relationship. We hypothesize that if HDV plays a role in the development of SjD, then HDV profiles may be correlated with disease manifestations. This retrospective study characterized HDV in a cohort of 48 SjD MSG samples collected between 2014 and 2021. Analyses of HDAg expression, including cell type and subcellular localization, in situ hybridization of HDV RNA, and comparative analyses with associated SjD and viral hepatitis clinical features, were conducted. HDAg was detected in MSG acinar, ductal, myoepithelial, and adipose cells and localized with the nuclei, cytoplasm, and mitochondria. In situ hybridization detected HDV genomic RNA localization in the MSG nuclei. A significant negative correlation was found between HDAg intensity and focal lymphocytic inflammation and in patients with both anti-SSA/Ro-52 and anti-SSA/Ro-60. In analyzing autoimmune disease comorbidities with SjD, it was found that SjD patients diagnosed with autoimmune thyroiditis and/or hypothyroidism were significantly more represented in the high HDAg intensity group compared to the negative and moderate HDAg intensity groups. No significant associations were detected between MSG-localized HDAg and liver enzymes or an evident HBV coinfection. This study has further confirmed that there is a nonhepatic reservoir for chronic HDV persistence in SjD-affected salivary gland tissue in a third independent SjD patient cohort. In addition, this study describes the unique colocalization of HDAg with mitochondria. The detection of HDV antigen and sequence within SjD-affected salivary gland tissue, and in the absence of an evident current or past HBV coinfection, warrants further investigation.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":" ","pages":"1272-1279"},"PeriodicalIF":5.7,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10626587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10136434","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}

{"title":"Mutations Causing X-Linked Amelogenesis Imperfecta Alter miRNA Formation from Amelogenin Exon4.","authors":"R Shemirani, M H Le, Y Nakano","doi":"10.1177/00220345231180572","DOIUrl":"10.1177/00220345231180572","url":null,"abstract":"<p><p>Amelogenin plays a crucial role in tooth enamel formation, and mutations on X-chromosomal amelogenin cause X-linked amelogenesis imperfecta (AI). Amelogenin pre-messenger RNA (mRNA) is highly alternatively spliced, and during alternative splicing, exon4 is mostly skipped, leading to the formation of a microRNA (miR-exon4) that has been suggested to function in enamel and bone formation. While delivering the functional variation of amelogenin proteins, alternative splicing of exon4 is the decisive first step to producing miR-exon4. However, the factors that regulate the splicing of exon4 are not well understood. This study aimed to investigate the association between known mutations in exon4 and exon5 of X chromosome amelogenin that causes X-linked AI, the splicing of exon4, and miR-exon4 formation. Our results showed mutations in exon4 and exon5 of the amelogenin gene, including c.120T>C, c.152C>T, c.155C>G, and c.155delC, significantly affected the splicing of exon4 and subsequent miR-exon4 production. Using an amelogenin minigene transfected in HEK-293 cells, we observed increased inclusion of exon4 in amelogenin mRNA and reduced miR-exon4 production with these mutations. In silico analysis predicted that Ser/Arg-rich RNA splicing factor (SRSF) 2 and SRSF5 were the regulatory factors for exon4 and exon5 splicing, respectively. Electrophoretic mobility shift assay confirmed that SRSF2 binds to exon4 and SRSF5 binds to exon5, and mutations in each exon can alter SRSF binding. Transfection of the amelogenin minigene to LS8 ameloblastic cells suppressed expression of the known miR-exon4 direct targets, <i>Nfia</i> and <i>Prkch</i>, related to multiple pathways. Given the mutations on the minigene, the expression of <i>Prkch</i> has been significantly upregulated with c.155C>G and c.155delC mutations. Together, we confirmed that exon4 splicing is critical for miR-exon4 production, and mutations causing X-linked AI in exon4 and exon5 significantly affect exon4 splicing and following miR-exon4 production. The change in miR-exon4 would be an additional etiology of enamel defects seen in some X-linked AI.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":" ","pages":"1210-1219"},"PeriodicalIF":7.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2a/a4/10.1177_00220345231180572.PMC10548775.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9971884","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}

{"title":"Developing Bioactive Dental Resins for Restorative Dentistry.","authors":"M A S Melo, I M Garcia, L Mokeem, M D Weir, H H K Xu, C Montoya, S Orrego","doi":"10.1177/00220345231182357","DOIUrl":"10.1177/00220345231182357","url":null,"abstract":"<p><p>Despite its reputation as the most widely used restorative dental material currently, resin-based materials have acknowledged shortcomings. As most systematic survival studies of resin composites and dental adhesives indicate, secondary caries is the foremost reason for resin-based restoration failure and life span reduction. In subjects with high caries risk, the microbial community dominated by acidogenic and acid-tolerant bacteria triggers acid-induced deterioration of the bonding interface and/or bulk material and mineral loss around the restorations. In addition, resin-based materials undergo biodegradation in the oral cavity. As a result, the past decades have seen exponential growth in developing restorative dental materials for antimicrobial applications addressing secondary caries prevention and progression. Currently, the main challenge of bioactive resin development is the identification of efficient and safe anticaries agents that are detrimental free to final material properties and show satisfactory long-term performance and favorable clinical translation. This review centers on the continuous efforts to formulate novel bioactive resins employing 1 or multiple agents to enhance the antibiofilm efficacy or achieve multiple functionalities, such as remineralization and antimicrobial activity antidegradation. We present a comprehensive synthesis of the constraints and challenges encountered in the formulation process, the clinical performance-related prerequisites, the materials' intended applicability, and the current advancements in clinical implementation. Moreover, we identify crucial vulnerabilities that arise during the development of dental materials, including particle aggregation, alterations in color, susceptibility to hydrolysis, and loss of physicomechanical core properties of the targeted materials.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":" ","pages":"1180-1190"},"PeriodicalIF":5.7,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11066520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9960704","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}

{"title":"Dental Medicine and Engineering Unite to Transform Oral Health Innovations.","authors":"H Koo, K Stebe","doi":"10.1177/00220345231183339","DOIUrl":"10.1177/00220345231183339","url":null,"abstract":"<p><p>This perspective article urges the academic community to adopt a coordinated approach uniting dental medicine and engineering to support research, training, and entrepreneurship to address the unmet needs and spur oral health care innovations. We describe a new interschool institute that brings together dentists, scientists and engineers, resources, and a training program dedicated for affordable oral health care innovations, which may serve as a template for dental medicine-engineering integration.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":" ","pages":"1177-1179"},"PeriodicalIF":7.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/76/2a/10.1177_00220345231183339.PMC10548769.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9947572","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}

{"title":"Fibulin-1 Regulates Initiation of Successional Dental Lamina.","authors":"G Li,&nbsp;Q Li,&nbsp;Z Shen,&nbsp;X Lin,&nbsp;X Li,&nbsp;J Wang,&nbsp;B Zhao,&nbsp;Y Feng,&nbsp;L Feng,&nbsp;W Guo,&nbsp;L Hu,&nbsp;J Wang,&nbsp;C Zhang,&nbsp;Z Fan,&nbsp;S Wang,&nbsp;X Wu","doi":"10.1177/00220345231182052","DOIUrl":"10.1177/00220345231182052","url":null,"abstract":"<p><p>In humans, teeth are replaced only once, and the successional dental lamina (SDL) of the permanent tooth is maintained in a quiescent state until adolescence. Recently, we showed that biomechanical stress generated by the rapid growth of the deciduous tooth inhibits SDL development via integrin β1-RUNX2 signaling at embryonic day 60 (E60) in miniature pigs. However, the mechanism by which RUNX2 regulates SDL initiation within the SDL stem cell niche remains unclear. In the current study, we transcriptionally profiled single cells from SDL and surrounding mesenchyme at E60 and identified the landscape of cellular heterogeneity. We then identified a specific fibroblast subtype in the dental follicle mesenchyme between the deciduous tooth and the SDL of the permanent tooth (DFDP), which constitutes the inner part of the niche (deciduous tooth side). Compared with traditional dental follicle cells, the specific expression profile of DFDP was identified and found to be related to biomechanical stress. Subsequently, we found that RUNX2 could bind to the enhancer regions of <i>Fbln1</i> (gene of fibulin-1), one of the marker genes for DFDP. Through gain- and loss-of-function experiments, we proved that the biomechanical stress-mediated RUNX2-fibulin-1 axis inhibits the initiation of SDL by maintaining SDL niche homeostasis.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":" ","pages":"1220-1230"},"PeriodicalIF":7.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9832284","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}

{"title":"CREB3L2 Regulates Hemidesmosome Formation during Epithelial Sealing.","authors":"Y Li,&nbsp;J Zhang,&nbsp;W Cai,&nbsp;C Wang,&nbsp;Z Yu,&nbsp;Z Jiang,&nbsp;K Lai,&nbsp;Y Wang,&nbsp;G Yang","doi":"10.1177/00220345231176520","DOIUrl":"10.1177/00220345231176520","url":null,"abstract":"<p><p>The long-term success rate of dental implants can be improved by establishing a favorable biological sealing with a high-quality epithelial attachment. The application of mesenchymal stem cells (MSCs) holds promise for facilitating the soft tissue integration around implants, but the molecular mechanism is still unclear and the general application of MSC sheet for soft tissue integration is also relatively unexplored. We found that gingival tissue-derived MSC (GMSC) sheet treatment significantly promoted the expression of hemidesmosome (HD)-related genes and proteins in gingival epithelial cells (GECs). The formation of HDs played a key role in strengthening peri-implant epithelium (PIE) sealing. Further, high-throughput transcriptome sequencing showed that GMSC sheet significantly upregulated the PI3K/AKT pathway, confirming that cell adhesion and HD expression in GECs were regulated by GMSC sheet. We observed that the expression of transcription factor CREB3L2 in GECs was downregulated. After treatment with PI3K pathway inhibitor LY294002, CREB3L2 messenger RNA and protein expression levels were upregulated. Further experiments showed that overexpression or knockdown of CREB3L2 could significantly inhibit or promote HD-related genes and proteins, respectively. We confirmed that CREB3L2 was a transcription factor downstream of the PI3K/AKT pathway and participated in the formation of HDs regulated by GMSC sheet. Finally, through the establishment of early implant placement model in rats, we clarified the molecular function of CREB3L2 in PIE sealing as a mechanical transmission molecule in GECs. The application of GMSC sheet-implant complex could enhance the formation of HDs at the implant-PIE interface and decrease the penetration distance of horseradish peroxidase between the implant and PIE. Meanwhile, GMSC sheet reduced the length of CREB3L2 protein expression on PIE. These findings elucidate the potential function and molecular mechanism of MSC sheet regulating the epithelial sealing around implants, providing new insights and ideas for the application of stem cell therapy in regenerative medicine.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":" ","pages":"1199-1209"},"PeriodicalIF":7.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9957927","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}

{"title":"Linking the Mechanics of Chewing to Biology of the Junctional Epithelium.","authors":"X Yuan, B Liu, P Cuevas, J Brunski, F Aellos, J Petersen, T Koehne, S Bröer, R Grüber, A LeBlanc, X Zhang, Q Xu, J A Helms","doi":"10.1177/00220345231185288","DOIUrl":"10.1177/00220345231185288","url":null,"abstract":"<p><p>The capacity of a tissue to continuously alter its phenotype lies at the heart of how an animal is able to quickly adapt to changes in environmental stimuli. Within tissues, differentiated cells are rigid and play a limited role in adapting to new environments; however, differentiated cells are replenished by stem cells that are defined by their phenotypic plasticity. Here we demonstrate that a Wnt-responsive stem cell niche in the junctional epithelium is responsible for the capability of this tissue to quickly adapt to changes in the physical consistency of a diet. Mechanical input from chewing is required to both establish and maintain this niche. Since the junctional epithelium directly attaches to the tooth surface via hemidesmosomes, a soft diet requires minimal mastication, and consequently, lower distortional strains are produced in the tissue. This reduced strain state is accompanied by reduced mitotic activity in both stem cells and their progeny, leading to tissue atrophy. The atrophied junctional epithelium exhibits suboptimal barrier functions, allowing the ingression of bacteria into the underlying connective tissues, which in turn trigger inflammation and mild alveolar bone loss. These data link the mechanics of chewing to the biology of tooth-supporting tissues, revealing how a stem cell niche is responsible for the remarkable adaptability of the junctional epithelium to different diets.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":" ","pages":"1252-1260"},"PeriodicalIF":5.7,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10626588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10014117","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}

{"title":"An Appreciation of a Giant in Orofacial Sciences Research-John Greenspan.","authors":"S J Challacombe,&nbsp;O D Klein","doi":"10.1177/00220345231181536","DOIUrl":"https://doi.org/10.1177/00220345231181536","url":null,"abstract":"<p><p>Professor John S. Greenspan died on March 31, 2023. He was a renowned and accomplished academic, dentist/scientist, pathologist, and administrator who made sustained and significant international impacts on numerous fields over half a century. John was arguably best known for his work with his wife, Dr. Deborah Greenspan, on the oral aspects of AIDS and the role of viruses in oral epithelial and salivary gland lesions. He had a lifelong interest in Sjögren's syndrome, culminating in the leadership of the Sjögren's International Collaborative Clinical Alliance. He was also widely recognized as one of the leading investigators into the understanding of oral mucosal diseases, including recurrent aphthous stomatitis. He and his colleagues' major contributions to HIV research and care included the discovery of the oral lesion \"hairy leukoplakia,\" its etiological association with Epstein-Barr virus, and other oral lesions in the natural history of HIV disease. In recent years, John turned his attention to global oral health inequalities, helping to establish the International Association for Dental Research's Global Oral Health Inequalities Research Network and serving as its first president. He led many organizations with humble authority, knowledge, wit, and wisdom and mentored colleagues from all over the world, especially from lower- and middle-income countries. John leaves a very special legacy based on example and scientific curiosity, and his work has not only made a lasting impact on his colleagues but also translated to abiding benefit for patients.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"102 10","pages":"1073-1077"},"PeriodicalIF":7.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10039941","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}

{"title":"Tmem2 Deficiency Leads to Enamel Hypoplasia and Soft Enamel in Mouse.","authors":"P Nag,&nbsp;T Inubushi,&nbsp;J I Sasaki,&nbsp;T Murotani,&nbsp;S Kusano,&nbsp;Y Nakanishi,&nbsp;Y Shiraishi,&nbsp;H Kurosaka,&nbsp;S Imazato,&nbsp;Y Yamaguchi,&nbsp;T Yamashiro","doi":"10.1177/00220345231182355","DOIUrl":"https://doi.org/10.1177/00220345231182355","url":null,"abstract":"<p><p>Teeth consist of 3 mineralized tissues: enamel, dentin, and cementum. Tooth malformation, the most common craniofacial anomaly, arises from complex genetic and environmental factors affecting enamel structure, size, shape, and tooth eruption. Hyaluronic acid (HA), a primary extracellular matrix component, contributes to structural and physiological functions in periodontal tissue. Transmembrane protein 2 (TMEM2), a novel cell surface hyaluronidase, has been shown to play a critical role during embryogenesis. In this study, we demonstrate <i>Tmem2</i> messenger RNA expression in inner enamel epithelium and presecretory, secretory, and mature ameloblasts. <i>Tmem2</i> knock-in reporter mice reveal TMEM2 protein localization at the apical and basal ends of secretory ameloblasts. Micro-computed tomography analysis of epithelial-specific <i>Tmem2</i> conditional knockout (<i>Tmem2</i>-<i>CKO</i>) mice shows a significant reduction in enamel layer thickness and severe enamel deficiency. Enamel matrix protein expression was remarkably downregulated in <i>Tmem2</i>-<i>CKO</i> mice. Scanning electron microscopy of enamel from <i>Tmem2</i>-<i>CKO</i> mice revealed an irregular enamel prism structure, while the microhardness and density of enamel were significantly reduced, indicating impaired ameloblast differentiation and enamel matrix mineralization. Histological evaluation indicated weak adhesion between cells and the basement membrane in <i>Tmem2</i>-<i>CKO</i> mice. The reduced and irregular expressions of vinculin and integrin β1 suggest that <i>Tmem2</i> deficiency attenuated focal adhesion formation. In addition, abnormal HA accumulation in the ameloblast layer and weak claudin 1 immunoreactivity in <i>Tmem2</i>-<i>CKO</i> mice indicate impaired tight junction gate function. Irregular actin filament assembly was also observed at the apical and basal ends of secretory ameloblasts. Last, we demonstrated that <i>Tmem2</i>-deficient mHAT9d mouse ameloblasts exhibit defective adhesion to HA-containing substrates in vitro. Collectively, our data highlight the importance of TMEM2 in adhesion to HA-rich extracellular matrix, cell-to-cell adhesion, ameloblast differentiation, and enamel matrix mineralization.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"102 10","pages":"1162-1171"},"PeriodicalIF":7.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10044514","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}

{"title":"Inhibition of Mertk Signaling Enhances Bone Healing after Tooth Extraction.","authors":"A M Decker, M Matsumoto, J T Decker, A Roh, N Inohara, J Sugai, K Martin, R Taichman, D Kaigler, L D Shea, G Núñez","doi":"10.1177/00220345231177996","DOIUrl":"10.1177/00220345231177996","url":null,"abstract":"<p><p>Regeneration of alveolar bone is an essential step in restoring healthy function following tooth extraction. Growth of new bone in the healing extraction socket can be variable and often unpredictable when systemic comorbidities are present, leading to the need for additional therapeutic targets to accelerate the regenerative process. One such target is the TAM family (Tyro3, Axl, Mertk) of receptor tyrosine kinases. These proteins have been shown to help resolve inflammation and maintain bone homeostasis and thus may have therapeutic benefits in bone regeneration following extraction. Treatment of mice with a pan-TAM inhibitor (RXDX-106) led to accelerated alveolar bone fill following first molar extraction in a mouse model without changing immune infiltrate. Treatment of human alveolar bone mesenchymal stem cells with RXDX-106 upregulated Wnt signaling and primed the cells for osteogenic differentiation. Differentiation of human alveolar bone mesenchymal stem cells with osteogenic media and TAM-targeted inhibitor RXDX-106 (pan-TAM), ASP-2215 (Axl specific), or MRX-2843 (Mertk specific) showed enhanced mineralization with pan-TAM or Mertk-specific inhibitors and no change with Axl-specific inhibitor. First molar extractions in Mertk^-/- mice had increased alveolar bone regeneration in the extraction socket relative to wild type controls 7 d postextraction. Flow cytometry of 7-d extraction sockets showed no difference in immune cell numbers between Mertk<i>^-/-</i> and wild type mice. RNAseq of day 7 extraction sockets showed increased innate immune-related pathways and genes associated with bone differentiation in Mertk<i>^-/-</i> mice. Together, these results indicate that TAM receptor signaling, specifically through Mertk, can be targeted to enhance bone regeneration after injury.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"102 10","pages":"1131-1140"},"PeriodicalIF":5.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10044805","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}