optimization-ligature-induced-periodontitis-mouse-model-for

Optimization of the Ligature-induced Periodontitis Mouse Model for Preclinical Research

The experimental model of ligature-induced periodontitis in mice has played a fundamental role in understanding periodontal disease pathogenesis; yet, it ...

Indiana University

This study examined the utility of stationary intraoral tomosynthesis (s-IOT) in opening proximal contacts in bitewing radiography.

The role of stationary intraoral tomosynthesis in reducing proximal overlap in bitewing radiography.

Diabetes is highly prevalent worldwide, with an estimated 536 million living with diabetes in 2021, and that number projected to increase to 783 million by 2045. Diabetic bladder dysfunction is thought to affect up to 60%-90% of individuals with diabetes and can significantly impact quality of life. Despite the prevalence of diabetic bladder dysfunction, the exact pathophysiological mechanism, and resulting clinical presentation, remains debated. Our objective was to compare urodynamic parameters between diabetic and nondiabetic women, assessing the impact of various markers of diabetes severity on bladder function.

An analysis of urodynamic parameters in diabetic and nondiabetic women.

Clonal hematopoiesis of indeterminate potential (CHIP) arises from aging-associated acquired mutations in hematopoietic progenitors, which display clonal expansion and produce phenotypically altered leukocytes. We associated CHIP-DNMT3A mutations with a higher prevalence of periodontitis and gingival inflammation among 4,946 community-dwelling adults. To model DNMT3A-driven CHIP, we used mice with the heterozygous loss-of-function mutation R878H, equivalent to the human hotspot mutation R882H. Partial transplantation with Dnmt3a bone marrow (BM) cells resulted in clonal expansion of mutant cells into both myeloid and lymphoid lineages and an elevated abundance of osteoclast precursors in the BM and osteoclastogenic macrophages in the periphery. DNMT3A-driven clonal hematopoiesis in recipient mice promoted naturally occurring periodontitis and aggravated experimentally induced periodontitis and arthritis, associated with enhanced osteoclastogenesis, IL-17-dependent inflammation and neutrophil responses, and impaired regulatory T cell immunosuppressive activity. DNMT3A-driven clonal hematopoiesis and, subsequently, periodontitis were suppressed by rapamycin treatment. DNMT3A-driven CHIP represents a treatable state of maladaptive hematopoiesis promoting inflammatory bone loss.

Clonal hematopoiesis driven by mutated DNMT3A promotes inflammatory bone loss.

Poor oral health can impact overall health. This study assessed the association between dental factors (dentate status and dental utilization) and self-rated health (S-RH) among older adults in two cross-sectional datasets: (1) NIH "All of Us (AoU) Research Program" (May 2018-July 2022 release) and (2) U.S. nationally representative "Health and Retirement Study" (HRS) 2018 wave. Participants aged ≥ 51 years were included in these analyses if (1) from AoU, they had clinical dental and medical data from electronic health records (EHRs) and surveys (n = 5480), and (2) from HRS, they had dental and socio-demographic survey data (n = 14,358). S-RH was dichotomized (fair/poor vs. better) and analyzed with logistic regression. Sample survey weights for HRS and stratification and averaging AoU results used the weighted HRS race-ethnicity and age distribution standardized respective analyses to the U.S. population. Fair/poor S-RH was reported by 32.6% in AoU and 28.6% in HRS. Dentate status information was available from 7.7% of AoU EHRs. In population-standardized analyses, lack of dental service use increased odds of fair/poor S-RH in AoU, OR (95% CI) = 1.28 (1.11-1.48), and in HRS = 1.45 (1.09-1.94), as did having diabetes, less education, and ever being a smoker. Having no natural teeth was not statistically associated with fair/poor S-RH. Lack of dental service was positively associated with fair/poor S-RH in both datasets. More and better oral health information in AoU and HRS are needed.

A Comparative Analysis of Oral Health and Self-Rated Health: 'All of Us Research Program' vs. 'Health and Retirement Study'.

To investigate the prevalence trend of gastroschisis in the United States between 2014 and 2022.

Decreasing trend of gastroschisis prevalence in the United States from 2014 through 2022: Is attributed to declining birth rates in young, high-risk gravidae.

Type I interferons (IFNs-I), a group of pleiotropic cytokines, critically modulate host response in various inflammatory diseases. However, the role of the IFN-I pathway in periodontitis remains largely unknown. In this report, we describe that the IFN-β levels in the gingival crevicular fluid of human subjects were negatively associated with periodontitis and clinical gingival inflammation. Disruption of IFN-I signaling worsened alveolar bone resorption in a ligature-induced periodontitis murine model. Deficiency of the IFN-I pathway resulted in an exaggerated inflammatory response in myeloid cells and drastically increased the interleukin-17 (IL-17)-mediated neutrophil recruitment in the gingiva. We further identified that the myeloid lineage-specific IFN-I response was essential in safeguarding against periodontal inflammation by suppressing the IL-17-producing γδ T cells in gingiva. IFN-I signaling also directly repressed osteoclastogenesis in monocytes, which are precursor cells for osteoclasts. Therefore, our findings demonstrate that an integral myeloid-specific IFN-I pathway protects against bone loss by keeping the IL-17-neutrophil axis in check and directly inhibiting osteoclast formation in periodontitis.

Type I interferon protects against bone loss in periodontitis by mitigating an interleukin (IL)-17-neutrophil axis.

Environmental exposures, such as pesticides, during pregnancy have been associated with several adverse pregnancy outcomes, including miscarriage and shorter gestational length at birth. However, their relationship with gestational diabetes (GDM) is uncertain. The objective of this study was to analyze first-trimester urinary herbicide concentrations for their associations with GDM.

First trimester urine glyphosate concentrations and gestational diabetes in nulliparas: a nested case-control study.

Inflammasome initiates inflammation via the maturation of interleukin-1 beta (IL-1β). Periodontitis is a prevalent, male-biased disease characterized by inflammation-driven bone loss, yet the mechanism(s) of this sex bias is unknown. This study explored whether enhanced inflammasome represents a causal mechanism for this bias. Analyses of three separate human studies (>6,200 samples) show that males have significantly higher IL-1β in the gingival crevicular fluid than females during health and periodontitis. This pattern is experimentally reproduced with different versions of the ligature-induced periodontitis mouse model where males show greater IL-1β secretion than females. The inflammasome drives bone resorption in males but not females as revealed by analyses of inflammasome gene-deletion mice. Pharmacologic treatment with a caspase-1/4 inhibitor reduces inflammatory cell infiltration, dampens osteoclastogenesis signaling (via the receptor activator of nuclear factor-kappa B pathway), and prevents bone resorption in males but not females during experimental periodontitis. While ovariectomized females show no change in their nonresponsiveness to caspase-1/4 inhibition, orchiectomized males no longer respond to the inhibition, suggesting the importance of an intact male reproductive system in the mediation of this inhibition. Thus, our study identifies inflammasome activation as causal for male-biased experimental periodontitis and supports sex-stratified studies to foster future advancement of inflammasome therapeutics in periodontics.

Inflammasome targeting for periodontitis prevention is sex dependent.

To add to the knowledge base of periodontal genomics, we carried out a genome-wide association study (GWAS) of periodontitis severity and progression among 416 mixed-ethnicity adult participants of a periodontitis clinical study.

Genome-wide association study of periodontitis severity and progression.

Urethral Bulkamid is a U.S. Food and Drug Administration-approved nonsurgical treatment for stress urinary incontinence and stress-predominant mixed urinary incontinence due to intrinsic sphincter deficiency. This procedure is commonly performed in the operating room (OR). An office Bulkamid procedure offers an alternative with benefits, including reduced cost, increased accessibility, and avoidance of anesthesia. Urinary retention is a known complication of Bulkamid. Data comparing retention rates between OR and office settings remains limited.

Effect of Procedure Setting on Urinary Retention After Bulkamid Injection.

Prior studies have demonstrated an association between oral infection and both incident stroke and atrial fibrillation (AF), a major cause of cardioembolic stroke. However, the impact of preventive oral behaviors such as dental flossing on incident stroke and AF remains unclear. We evaluated the relationship between flossing, incident stroke subtypes, and AF from the ARIC study (Atherosclerosis Risk in Communities).

Article	Year
The role of stationary intraoral tomosynthesis in reducing proximal overlap in bitewing radiography. Dento maxillo facial radiology\| PubMed ID: 32202939	2020
An analysis of urodynamic parameters in diabetic and nondiabetic women. Neurourology and urodynamics\| PubMed ID: 38808694	2024
Clonal hematopoiesis driven by mutated DNMT3A promotes inflammatory bone loss. Cell\| PubMed ID: 38838669	2024
A Comparative Analysis of Oral Health and Self-Rated Health: 'All of Us Research Program' vs. 'Health and Retirement Study'. International journal of environmental research and public health\| PubMed ID: 39338093	2024
Decreasing trend of gastroschisis prevalence in the United States from 2014 through 2022: Is attributed to declining birth rates in young, high-risk gravidae. European journal of obstetrics & gynecology and reproductive biology: X\| PubMed ID: 40027876	2025
Type I interferon protects against bone loss in periodontitis by mitigating an interleukin (IL)-17-neutrophil axis. Life sciences\| PubMed ID: 40086745	2025
First trimester urine glyphosate concentrations and gestational diabetes in nulliparas: a nested case-control study. Environmental health : a global access science source\| PubMed ID: 41057879	2025
Inflammasome targeting for periodontitis prevention is sex dependent. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 41144672	2025
Genome-wide association study of periodontitis severity and progression. Journal of periodontology\| PubMed ID: 41403351	2026
Effect of Procedure Setting on Urinary Retention After Bulkamid Injection. Urogynecology (Philadelphia, Pa.)\| PubMed ID: 41854464	2026
Dental Flossing May Lower the Risk for Incident Ischemic Stroke, Cardioembolic Stroke Subtype, and Atrial Fibrillation. Stroke\| PubMed ID: 41948826	2026

Kevin Moss

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