Journal of Dental Research最新文献

{"title":"In-depth Occlusion of Dentinal Tubules Induced by Polyaspartic Acid–Calcium and Magnesium Complexes","authors":"D. Shen, H. Zhu, Y. Xu, Z. Zhou, Z. Wu, B. Fu","doi":"10.1177/00220345241309340","DOIUrl":"https://doi.org/10.1177/00220345241309340","url":null,"abstract":"Dentin hypersensitivity has been widely recognized to be caused by patent dentinal tubules (DTs). A polyaspartic acid–calcium and magnesium (PAsp-Ca&Mg) complex process has been demonstrated to induce biomimetic mineralization of collagen fibrils. This study investigated the in vitro and in vivo occlusion of the DTs by a PAsp-Ca&Mg complex process. Dentin disks were treated by citric acid to open the DTs and randomly divided into 4 groups. Two experimental groups ( n = 18) were applied with PAsp-Ca&Mg suspension and phosphate solution or phosphate-fluoride solution in sequence for 10 min. Two positive control groups ( n = 18) were treated with Gluma or Duraphat. All the dentin disks were incubated in artificial saliva for 24 h. DT occlusion was characterized by scanning electron microscopy, and dentin permeability measurement was conducted regardless of being subject to abrasive or ultrasonic and acidic challenge. The incisors of 3 New Zealand rabbits were used to verify the in vivo occlusion of the DTs. In vitro and in vivo results demonstrated in-depth occlusion of the DTs to ~100 μm by the PAsp-Ca&Mg complex process. When compared with control groups, the PAsp-Ca&Mg complex process could significantly reduce dentin permeability ( P < 0.05) irrespective of abrasive or ultrasonic and acidic challenge. The PAsp-Ca&Mg complex process not only deeply occluded patent DTs but also significantly decreased dentin permeability and provided a paradigm for ion-doped DT occlusion. This provides a promising strategy for managing dentin hypersensitivity.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"82 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417384","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":"Microbial Dysbiosis, Titanium Release, and Peri-implantitis","authors":"G.A. Kotsakis, S.M. Ganesan","doi":"10.1177/00220345241307939","DOIUrl":"https://doi.org/10.1177/00220345241307939","url":null,"abstract":"The peri-implant mucosal barrier is a unique microenvironment where host-microbiome interactions take place on the surface of an implanted biomaterial. Therefore, peri-implant immunity not only is quintessential to oral health but also contributes to the maintenance of the biomaterial-tissue equilibrium in health. This review delves into the intricate interplay between host factors, biomaterial properties, and the microbiome with a focus on the mechanisms underlying peri-implant dysbiosis. Investigations into this complex milieu have led to the emerging understanding of titanium particles released from the implant as significant exposomes. When biomaterial breakdown occurs, implant degradation products form particles that are released in the peri-implant crevice, exerting profound effects on the local immune surveillance. Comparative analyses with natural dentition highlight the distinct immune responses elicited by titanium particles, thereby implicating them as a key modulator of peri-implant dysbiosis that differentiates peri-implant from periodontal inflammation. Nonetheless, disruptions in the homeostatic balance of host-biomaterial interactions are linked to pathogenic shifts of the peri-implant microbiome that are correlated with titanium particles in humans. Collectively, it is now well established that to elucidate the mechanisms governing peri-implant dysbiosis, this triangle of host-microbiome-biomaterial has to be conjointly investigated. This review highlights findings from studies that have underscored the multifaceted nature of peri-implant dysbiosis, emphasizing the intricate crosstalk between host immunity, biomaterial characteristics, and microbial ecology. These findings suggest that the titanium particle exposome may alter key inflammatory cascades in the peri-implant tissues including toll-like receptor activation and inflammasome and complement signaling, which lead to nonresolving destructive inflammation. The presence of abiotic danger signals in the form of implant degradation products in peri-implant tissues may make antimicrobial monotherapies largely ineffective for managing peri-implantitis. In turn, the future of peri-implantitis therapy seems to lie in the development of targeted host modulatory interventions against titanium-mediated inflammatory pathways.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"63 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417383","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":"Discrimination and Oral Health Impact: Moderating Role of Sex and Sexuality","authors":"G.H. Soares, S. Sethi, A. Jessani, L. Jamieson","doi":"10.1177/00220345241310223","DOIUrl":"https://doi.org/10.1177/00220345241310223","url":null,"abstract":"This study investigated whether sex assigned at birth and sexuality have a moderating role on the effect of discrimination on oral health impacts among adolescents. Using data from the Longitudinal Study of Australian Children, a sample representative of all Australian adolescents aged 14 to 15 y ( N = 2,905), we employed propensity score overlap weights to achieve covariate balance between participants exposed and unexposed to discrimination. Various forms of discrimination were examined: due to cultural background, due to mental health condition, due to sexual orientation, and due to sex assigned at birth. Oral health impact was assessed using the PedsQ Oral Health Scale. Poisson regression with robust variance was conducted including sex, sexual attraction, and discrimination as interaction terms. The sample included 1,407 females (49%) and 336 lesbian, gay, bisexual, and questioning (LGBQ) individuals (11%). More than 22% experienced at least 1 form of discrimination in the previous 6 mo. Findings from the overlap weighting analysis revealed that, in general, females had higher proportions of oral health impact compared with males, whereas sexually diverse youth tended to have worse oral health outcomes compared with non-LGBQ youth. A 2-fold higher prevalence rate of oral health impacts was found for sexually diverse females exposed to discrimination due to cultural background (95% confidence interval [CI]: 1.36–2.44) and due to mental health conditions (95% CI: 1.62–2.46). The largest effects of discrimination on oral health impacts were consistently observed among sexually diverse females. This novel study provides evidence on the moderating role of sex and sexuality in the relationship between discrimination and oral health among adolescents.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"42 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417385","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":"Tumor-Intrinsic SIRPA Drives Pyroptosis Evasion in Head and Neck Cancer","authors":"A. Song, Q.-C. Yang, W.-D. Wang, S. Wang, H. Li, L. Wu, Z.-J. Sun","doi":"10.1177/00220345241305590","DOIUrl":"https://doi.org/10.1177/00220345241305590","url":null,"abstract":"Pyroptosis, a gasdermin-mediated immunogenic cell death, has been shown to elicit adaptive antitumor immune responses, thereby augmenting the response to cancer immunotherapy when pyroptosis is therapeutically activated. However, despite increased gasdermin E (GSDME) expression, significant pyroptosis remains elusive in certain tumor types, and the underlying regulatory mechanisms are poorly understood. In this study, we observed high signal regulatory protein α1 (SIRPA) expression in head and neck squamous cell carcinoma (HNSCC) cells, a target in cancer immunotherapy. Intriguingly, SIRPA inhibition markedly augmented pyroptosis activity in tumor tissues and modulated tumor growth in a HNSCC mouse model. Subsequent investigations revealed that SIRPA knockout upregulated GSDME expression and potentiated cisplatin-induced pyroptosis in cancer cells. Integrative transcriptomics and metabolomics analysis suggested that the SIRPA knockout profoundly altered protein ubiquitination and augmented argininosuccinic acid levels in cancer cells. Specifically, we demonstrated that ubiquitin-specific peptidase 18 (USP18), a deubiquitinating enzyme, targets GSDME for deubiquitination and that USP18 knockdown suppressed cisplatin-induced pyroptosis. Notably, we found that succinylation of GSDME, which is mediated by succinyl-CoA, promotes GSDME cleavage without affecting caspase-3 activation. Further experiments indicated that SIRPA expression in tumor cells can decrease the antitumor efficacy of chemotherapy and immunotherapy in HNSCC mouse models. In summary, our findings reveal a novel mechanism of pyroptosis evasion in HNSCC, whereby tumor-intrinsic SIRPA enhances GSDME ubiquitylation and inhibits its succinylation. These insights suggest that inhibiting SIRPA expression may improve the efficacy of immunotherapy for HNSCC by inducing pyroptosis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"50 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143125233","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":"Unveiling the Etiopathogenic Role of Epstein-Barr Virus in Periodontitis","authors":"L. Tonoyan, C. Mounier, J. Fassy, S. Leymarie, S. Mouraret, P. Monneyron, S. Vincent-Bugnas, B. Mari, A. Doglio","doi":"10.1177/00220345241303138","DOIUrl":"https://doi.org/10.1177/00220345241303138","url":null,"abstract":"Periodontitis, a prevalent and costly oral disease, remains incompletely understood in its etiopathogenesis. The conventional model attributes it to pathogenic bacteria, but emerging evidence suggests dysbiosis involving bacteria, herpesviruses, and an exaggerated host immune response. Among herpesviruses, Epstein-Barr virus (EBV) closely links to severe periodontitis, yet the mechanisms underlying EBV-related pathogenesis remain elusive. This study examined the presence, methylation patterns, and infection states of EBV in gingival tissues from healthy patients and those with periodontitis. It also assessed gene expression differences associated with EBV through whole-genome transcriptomic profiling in healthy and periodontitis-affected tissues. EBV DNA was found at similar frequencies in healthy and periodontitis tissues, suggesting common EBV infection even before disease manifestation. In healthy tissues, mostly unmethylated EBV genomes indicated lytic infection in gums, consistent with the literature on lytic EBV spread in epithelia and continual significant virus release in the saliva of healthy carriers. Conversely, EBV DNA in periodontitis tissues showed both methylated and unmethylated patterns, suggesting a mix of latent and lytic genomes. This indicates the coexistence of latent EBV in B-cells and lytic EBV in plasma cells (PCs), linking EBV presence with both cell types in periodontitis. Whole-genome transcriptomic analysis revealed distinct expression profiles in EBV-positive periodontitis tissues, with upregulated genes associated with inflammatory/immune responses and B-cell and PC markers, while downregulated genes were related to epithelial structure and organization. The EBV-positive periodontitis signature differed distinctly from that of EBV-positive healthy gums, eliciting only a typical viral-induced immune response. These findings provide new insights into EBV physiopathology in the gum, notably assigning a direct etiopathogenetic contribution to EBV in periodontitis. The results suggest a model where EBV can commonly, and apparently asymptomatically, spread in healthy gingiva but may also aggravate inflammation in the context of gum dysbiosis, involving infiltration of B-cells and PCs and loss of epithelial integrity.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"26 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056497","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":"Imaging Brain Networks: Insights into Mechanisms of Temporomandibular Disorders","authors":"R. Zhao, Z. Ye, X. Lv, Z. Li, X. Xiong","doi":"10.1177/00220345241302046","DOIUrl":"https://doi.org/10.1177/00220345241302046","url":null,"abstract":"Temporomandibular disorders are a group of craniomaxillofacial disorders mainly characterized by pain and motor dysfunction of the temporomandibular joints and surrounding masticatory muscles. Clinically, patients with temporomandibular disorders often display central nervous system dysfunction, such as negative mood disorders, but the underlying cause remains unclear. Recent developments in neuroimaging techniques have facilitated new understanding. Notably, the triple network model consisting of the default mode network, the central executive network, and the salience network is of particular interest in this regard and may provide new insights into brain network alterations. Specifically, we observed that patients with temporomandibular disorders have abnormal activation of attention-related brain regions in the default mode network, which may be related to pain rumination. In addition, cortical atrophy and altered functional connectivity were found in regions related to the regulation of emotion and pain. In the central executive network, decreased activity and metabolism were seen in pain regulation regions, while abnormal activation occurred in regions associated with negative emotions. The salience network showed aberrant activation and metabolic changes in pain perception regions, and negative emotions were associated with an abnormal activation pattern. Potentially treatment-induced changes included a return to normal activity in attention and emotion regulation regions, suggesting that assessing activity in these networks may be used to evaluate treatment efficacy. Finally, this review highlights current dilemmas and future opportunities for the field in terms of research cohorts, methods, scope, and analytical techniques. Further exploration is necessary to realize a better understanding of the neuropathophysiology of temporomandibular disorders and ultimately more effective treatments.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"23 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056498","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":"Molecular Profiling of Odontoclasts during Physiological Tooth Replacement","authors":"J.I. Henriquez, S. Flibotte, K. Fu, J.M. Richman","doi":"10.1177/00220345241304756","DOIUrl":"https://doi.org/10.1177/00220345241304756","url":null,"abstract":"The odontoclast is a rarely studied cell type that is overly active in many dental pathologies, leading to tooth loss. It is difficult to find diphyodont mammals in which either physiological or pathological root resorption can be studied. Here we use the adult leopard gecko, which has repeated cycles of physiological tooth resorption and shedding. RNA-seq was carried out to compare gene expression profiles of functional teeth to developing teeth. Genes more highly expressed in bell-stage developing teeth were related to morphogenesis ( PTHLH, SFRP2, SHH, EDAR). Some genes expressed in osteoclasts ( ACP5, CTSK, CSF1R) were relatively more abundant in functional teeth compared with developing teeth. There was, however, no differential expression of RANK and RANKL in the 2 tooth types. In addition, functional teeth expressed proteolysis genes not found in osteoclasts ( ADAMTS2, 3, 4, 14; CTSA, CTSH, CTSS). We used tartrate acid resistant phosphatase and cathepsin K (CTSK) staining to identify odontoclasts in and around the gecko dentition. There were 3 populations of CTSK cells: (1) large, functional multinucleated odontoclasts in the crown of the tooth with a ruffled border inside resorption pits; (2) smaller, precursor cells in the pulp with fewer nuclei; and (3) flattened external precursor cells next to the root and bone of attachment. We found a positive relationship between developing teeth and the population of CTSK+ cells on the root surface. We tested a candidate signal that may be involved in CTSK+ cell presence. An antagonist of CSF1R was delivered to developing teeth in vivo, which resulted in a significant decrease in CTSK and CSF1R compared with DMSO controls. Thus, the CSF1 signaling pathway is upstream of CTSK in teeth. This is the first work to detail the molecular characteristics of odontoclasts during physiological tooth shedding and to demonstrate that in vivo, local drug delivery is possible in the gecko model.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"1 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056496","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":"Friction of Laser-Textured Zirconia Coated with a Platelet-Rich Fibrin","authors":"M. Noronha Oliveira, N. Sahoo, O. Carvalho, F.S. Silva, J. Gomes, M. Özcan, B. Henriques, J.C.M. Souza","doi":"10.1177/00220345241305318","DOIUrl":"https://doi.org/10.1177/00220345241305318","url":null,"abstract":"In the present in vitro study, we evaluated the adhesion of an injectable platelet-rich fibrin (i-PRF) to laser-textured zirconia surfaces and their resultant friction behavior against bone tissue. Three types of zirconia surfaces were compared regarding the i-PRF coating effects: 1) grit blasted with 250-μm spherical alumina particles and acid etched with 20% hydrofluoric acid (ZLA), 2) laser textured with a random (RD) surface pattern, or 3) laser textured with a designed pattern based on 16 lines and 8 passages (L16N8). The coefficient of friction (COF) of the specimens was assessed on a reciprocating sliding pin-on-plate tribometer at 1-N normal load, 1 Hz, and a 2-mm stroke length. Sliding wear tests were carried out against bovine femoral bone tissue in 0.9% sodium chloride solution at room temperature. Surfaces were then assessed by scanning electron microscopy. COF mean values for test groups (0.35, ZLA; 0.45, L16N8) were lower when compared with the control groups (0.52, ZLA; 0.60, L16N8), with the exception of the RD group (0.47, test; 0.43, control). Results did not show significant differences in COF mean values between RD and L16N8 surfaces after coating with i-PRF. The 3-dimensional fibrin network embedded with leukocytes, platelets, and red blood cells was responsible for decreasing COF mean values over the zirconia surfaces, thus providing a lubricant effect. Also, the morphologic aspects of the laser-treated zirconia surfaces increased the adhesion of the platelet-rich fibrin, which could speed up the osseointegration process of zirconia implants.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"53 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056502","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":"Trends in Research of Odontogenic Keratocyst and Ameloblastoma","authors":"X.-H. Liu, N.-N. Zhong, J.-R. Yi, H. Lin, B. Liu, Q.-W. Man","doi":"10.1177/00220345241282256","DOIUrl":"https://doi.org/10.1177/00220345241282256","url":null,"abstract":"Odontogenic keratocyst (OKC) and ameloblastoma (AM) are common jaw lesions with high bone-destructive potential and recurrence rates. Recent advancements in technology led to significant progress in understanding these conditions. Single-cell and spatial omics have improved insights into the tumor microenvironment and cellular heterogeneity in OKC and AM. Fibroblast subsets in OKC and tumor cell subsets in AM have been analyzed, revealing mechanisms behind their biological behaviors, including OKC’s osteolytic features and AM’s recurrence tendencies. Spatial transcriptomics studies of AM have identified engineered fibroblasts and osteoblasts contributing to matrix remodeling gene and oncogene expression at the invasion frontier, driving AM progression. Three-dimensional culture technologies such as organoid models have refined analysis of AM subtypes; uncovered the role of AM fibroblasts in promoting tumor cell proliferation and invasion; and identified signaling pathways such as FOSL1, BRD4, EZH2, and Wnt as potential therapeutic targets. Organoid models also served as preclinical platforms for testing potential therapies. Although preclinical models for AM exist, reliable in vitro and in vivo models for OKC remain scarce. Promising mimic models, including human embryonic stem cells–derived epithelial cells, human oral keratinocytes, human immortalized oral epithelial cells, and HaCaT keratinocytes, show promise, but the advancements in 3-dimensional culture technology are expected to lead to further breakthroughs in this area. Artificial intelligence, including machine learning and deep learning, has enhanced radiomics-based diagnostic accuracy, distinguishing OKC and AM beyond clinician capability. Pathomics-based models further predict OKC prognosis and differentiate AM from ameloblastic carcinoma. Clinical studies have shown positive outcomes with targeted therapies. In a study investigating SMO-targeted treatments for nevoid basal cell carcinoma syndrome, nearly all OKC lesions resolved in 3 patients. A recent clinical trial with neoadjuvant BRAF-targeted therapy for AM demonstrated promising radiologic responses, potentially enabling organ preservation. This review highlights recent advancements and trends in OKC and AM research, aiming to inspire further exploration and progress in these fields.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"20 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056493","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":"Chewing-Activated TRPV4/PIEZO1–HIF-1α–Zn Axes in a Rat Periodontal Complex","authors":"Y. Wang, B.H. Lee, Z. Yang, T.J. Ho, H. Ci, B. Jackson, T. Pushon, B. Wang, J. Levy, S.P. Ho","doi":"10.1177/00220345241294001","DOIUrl":"https://doi.org/10.1177/00220345241294001","url":null,"abstract":"The upstream mechanobiological pathways that regulate the downstream mineralization rates in periodontal tissues are limitedly understood. Herein, we spatially colocalized and correlated compression and tension strain profiles with the expressions of mechanosensory ion channels (MS-ion) TRPV4 and PIEZO1, biometal zinc, mitochondrial function marker ( MFN2), cell senescence indicator ( p16), and oxygen status marker hypoxia-inducible factor-1α ( HIF-1α) in rats fed hard and soft foods. The observed zinc and related cellular homeostasis in vivo were ascertained by TRPV4 and PIEZO1 agonists and antagonists on human periodontal ligament fibroblasts ex vivo. Four-week-old male Sprague-Dawley rats were fed hard ( n = 3) or soft ( n = 3) foods for 4 wk (in vivo). Significant changes in alveolar socket and root shapes with decreased periodontal ligament space and increased cementum volume fraction were observed in maxillae on reduced loads (soft food). Reduced loads impaired distally localized compression-stimulated PIEZO1 and mesially localized tension-stimulated TRPV4, decreased mitochondrial function ( MFN2), and increased cell senescence in mesial and distal periodontal regions. The switch in HIF-1α from hard food–distal to soft food–mesial indicated a plausible effect of shear-regulated blood and oxygen flows in the periodontal complex. Blunting or activating TRPV4 or PIEZO1 MS-ion channels by channel-specific antagonists or agonists in human periodontal ligament fibroblast cultures (in vitro) indicated a positive correlation between zinc levels and zinc transporters but not with MS-ion channel expressions. The effects of reduced chewing loads in vivo were analogous to TRPV4 and PIEZO1 antagonists in vitro. Study results collectively illustrated that tension-induced TRPV4 and compression-induced PIEZO1 activations are necessary for cell metabolism. An increased hypoxic state with reduced functional loads can be a conducive environment for cementum growth. From a practical standpoint, dose rate–controlled loads can modulate tension and compression-specific MS-ion channel activation, cellular zinc, and HIF-1α transcription. These mechanobiochemical events indicate the plausible catalytic role of biometal zinc in mineralization, periodontal maintenance, and dentoalveolar joint function.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"76 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056492","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}