Distinct cross talk of IL-17 & TGF-ß with the immature CD11c+ TRAF6(-/-) -null myeloid dendritic cell-derived osteoclast precursor (mDDOCp) may engage signaling toward an alternative pathway of osteoclastogenesis for arthritic bone loss in vivo.

BACKGROUND: Dendritic cells (DCs), though borne heterogeneous, are the most potent antigen-presenting cells, whose critical functions include triggering antigen-specific naïve T-cell responses and fine-tuning the innate versus adaptive immunity at the osteo-immune and/or mucosal mesenchyme interface. We previously reported that immature myeloid-CD11c+ DCs/mDCs may act like osteoclast (OC) precursors (OCp/mDDOCp) capable of developing into functional OCs via an alternative pathway of inflammation-induced osteoclastogenesis; however, what are their contribution and signaling interactions with key osteotropic cytokines (i.e., interleukin-17 [IL-17] and transforming growth factor-ß [TGF-ß]) to bearing such inflammatory bone loss in vivo remain unclear to date. METHODS: Herein, we employed mature adult bone marrow-reconstituted C57BL/6 TRAF6(-/-) -null chimeras without the classical monocyte/macrophage (Mo/Mϕ)-derived OCs to address their potential contribution to OCp/mDDOCp-mediated osteoclastogenesis in the chicken type-II-collagen (CC-II)-induced joint inflammation versus arthritic bone loss and parallel associations with the double-positive CD11c+ TRAP+ TRAF6-null(-/-)  DC-like OCs detected in vivo via the quantitative dual-immunohistochemistry and digital histomorphometry for analyses. RESULTS: The resulting findings revealed the unrecognized novel insight that (i) immature myeloid-CD11c+ TRAF6(-/-) TRAP+ DC-like OCs were involved, co-localized, and strongly associated with joint inflammation and bone loss, independent of the Mo/Mϕ-derived classical OCs, in CC-II-immunized TRAF6(-/-) -null chimeras, and (ii) the osteotropic IL-17 may engage distinct crosstalk with CD11c+ mDCs/mDDOCp before developing the CD11c+ TRAP+ TRAF6(-/-) OCs via a TGF-ß-dependent interaction toward inflammation-induced arthritic bone loss in vivo. CONCLUSION: These results confirm and substantiate the validity of TRAF6(-/-) -null chimeras to address the significance of immature mCD11c+ TRAP+ DC-like OCs/mDDOCp subset for an alternative pathway of arthritic bone loss in vivo. Such CD11c+ mDCs/mDDOCp-associated osteoclastogenesis through the step-wise twist-in-turns osteo-immune cross talks are thereby theme highlighted to depict a summative re-visitation proposed.

Potential contribution of immature myeloid CD11c+dendritic cells-derived osteoclast precursor to inflammation-induced bone loss in the TRAF6-null chimeras in-vivo.

Dendritic cells (DC) are potent antigen-presenting-cells widely distributed at the osteo-immune and/or mucosal-mesenchyme interface, consequentially implicating in certain bone-sparing disorders; i.e., via signaling Receptor-activator-of-nuclear-factor-kappa-B-ligand/RANKL-Receptor-activator-of-nuclear-factor-kB/RANK-Osteoprotegerin/OPG-TRAF6 transducer-complex etc., evidently associated with arthritis, osteoporosis and periodontitis. We have reported that the immature myeloid CD11c+-DC subsets can act as osteoclast precursor (OCp; mDDOCp), thereby developing into osteoclasts (OCs) via an alternative pathway for osteoclastogenesis. Importantly, cytokine TGF-ß remains critical to prime CD11c+-mDDOCp-cells deficient of TRAF6-&-related immune/osteotropic signaling, featuring distinctive TGF-ß-&-IL-17-invoked effectors in the environmental milieu sufficient to driving bona-fide osteoclastogenesis in-vitro. Herein, we sought to explore the potential contribution of immature-mDDOCp/OCp to inflammation-induced bone-loss, where comparable CD11c+TRAP+multinucleated-OC-like/mDDOCp existed, lacking the endogenous TRAF6-associated monocyte/macrophage-derived OCs in type-II-collagen induced joint/paw inflammation of the C56BL/6-TRAF6(-/-)null chimeras (H-2b-halpotype) examined. The results suggest that such TRAF6-null chimeric mice may offer a useful model to assess the specific functions of OCp or mDDOCp as an analog to human conditions in-vivo.

Early Childhood Caries Is Causally Attributed to Developing Psychomotor Deficiency in Pre-School Children: The Resultant Covariate and Confounder Analyses in a Longitudinal Cohort Study.

Background: Causality has recently been suggested to associate early childhood caries with psychomotor deficiency in preschoolers, where their causal interactions via other risk determinants remain unclear. Methods: To analyze such causality, we randomly recruited 123 three-to-six-year-old children in a three-year longitudinal study, where the caries/dmft measures, age/gender, BMI, amended comprehensive scales for psychomotor development (CCDI-aspects), parental education/vocation, and diet were collected for assessment of their inter-relationships. Subsequently, t-tests, multiple/linear-regressions, and R2-analyses were utilized to compare the differences of variables between age/gender, BMI, and dmft vs. relationships among all variables and CCDI-aspects. Results: In the regression modeling, there were significant differences between gender vs. age (p < 0.05; not BMI) regarding established associations between caries and CCDI manifests for psychomotor deficiency. As for diet vs. socio-economic status, there were significant differences when caries/dmft were at lower- vs. higher-scales (<4 and 6−10), associated with expressive language and comprehension-concept (p~0.0214−0.0417) vs. gross-motor and self-help (p~0.0134−0.0486), respectively. Moreover, diet vs. socio-economic-status contributed significantly different CCDI-spectra via expressive language and comprehension-concept (adjusted-R2~0.0220−0.2463) vs. gross-motor and self-help (adjusted-R2~0.0645−0.0994), respectively, when the caries detected were at lower- vs. higher-scales (<4 and 6−10), in contrast to those depicted without both SES diet variables (adjusted-R2~0.0641−0.0849). Conclusion: These new findings confirm that early childhood caries is causally attributed to developing psychomotor deficiency in preschoolers, whereas biological gender/age, not BMI, may act as viable confounders during interactions, in contrast to diet and socio-economic status, via differential low−high scales of caries activity with significant interference, respectively. Collectively, ECC-psychomotor interactions may underpin some distinct biologic vs. socio-mental/psyche attributes towards different determinants for vulnerable children.

Socio-Economic Status May Associate Different Risk(s) with Early Childhood Caries (ECC) That Can Cause the Development of Psychomotor Deficiency in Preschool Children Aged 3-6 Years Old: The Results of Preliminary Analysis from a Cohort Study.

BACKGROUND: We have recently shown that there is a positive correlation between severe caries and developing psychomotor deficiency in preschool children. To fully re-assess such a relationship, we embarked on a 3-year longitudinal follow-up study of kindergarteners, where we aimed to: (i) confirm whether early childhood caries is causally related to the development of psychomotor deficiency as proposed, and (ii) address any significant role or contribution of socio-economic status associated with caries-psychomotor interactions in the preschooler family cohorts studied, over time. METHODS: A longitudinal study was designed where the total sum of 159 kindergarteners aged 3-6 from the central and southern regions of Taiwan were randomly selected and recruited for clinical examination of caries, together with questionnaires for personal, demographic and dietary information, socio-economic status, and the children's psychomotor development scales which were collected and analyzed over time. Student's t test, chi-squared test, correlation coefficients, and multiple linear regression analysis with R2 determinants were employed to assess any attributable differences (of 0~1) between SES vs. psychomotor manifests and caries measured among all variables computed. RESULTS: The results of our preliminary analyses show that: (i) there was likely a causal relationship between caries activities and aspects of general development scale via the Chinese Child Development Inventory over time (4.01 ± 3.47 vs. 5.88 ± 2.58, respectively) in the 3-6-year-old preschoolers, and (ii) there was significantly more attributable influence (via higher R-squared values) from SES and psychomotor manifests than that of caries and the Chinese Child Development Inventory counterparts, as detected over time. CONCLUSION: Collectively, the resulting analyses support our previous findings and confirm that there is likely a causal relationship between severe caries and psychomotor deficiency in growing preschoolers; the resulting analyses revealed that such causally related interactions may be attributably explainable by a content-reliant association via socio-economic status analyzed in the kindergartener family cohorts studied. Thus, the socio-economic status or its constituents/factors will have a much broader influence not only associated with developing early childhood caries (a biologic trait), but also for psychomotor deficiency (a social trait) in vulnerable children at risk.

Update and review of the gerodontology prospective for 2020's: Linking the interactions of oral (hypo)-functions to health vs. systemic diseases.

New lines of evidence suggest that the oral-systemic medical links and oral hypo-function are progressively transcending beyond the traditional clinical signs and symptoms of oral diseases. Research into the dysbiotic microbiome, host immune/inflammatory regulations and patho-physiologic changes and subsequent adaptations through the oral-systemic measures under ageism points to pathways leading to mastication deficiency, dysphagia, signature brain activities for (neuro)-cognition circuitries, dementia and certain cancers of the digestive system as well. Therefore, the coming era of oral health-linked systemic disorders will likely reshape the future of diagnostics in oral geriatrics, treatment modalities and professional therapies in clinical disciplines. In parallel to these highlights, a recent international symposium was jointly held by the International Association of Gerontology and Geriatrics (IAGG), Japanese Society of Gerodontology (JSG), the representative of USA and Taiwan Academy of Geriatric Dentistry (TAGD) on Oct 25th, 2019. Herein, specific notes are briefly addressed and updated for a summative prospective from this symposium and the recent literature.

Higher Levels of Early Childhood Caries (ECC) Is Associated with Developing Psychomotor Deficiency: The Cross- Sectional Bi-Township Analysis for The New Hypothesis.

The aim of this study was to reassess and confirm the relationship between early childhood caries (ECC) and manifestations of psychomotor deficiency in 4-6-yr-old kindergarteners, which has remained elusive to date. A cross-sectional study with bi-township analysis was designed whereby 353 kindergarteners, aged 4-6 whose caries were greater (dmft (decayed, missing and filled teeth, dmft index) = 5.25) than that of the national average, located in a rural township of central Taiwan were recruited using simple random-selection. Besides the personal, demographic, and dietary information, the measurements for caries and the amended comprehensive scales (CCDI) of children's psychomotor development were used to address their relationship. One-way ANOVA vs. multiple linear regression were employed to compare the differences of variables between age, gender, BMI (Body Mass Index), and dmft scores vs. relationships among all variables, respectively. The results confirmed that there was a positive relationship between severe ECC (dmft > 3~8) and psychomotor deficiency (i.e., expressive language and comprehension-concept scales, etc.) amongst the kindergarteners analyzed. Our cross-sectional bi-township analysis has confirmed that there is indeed an association between severe ECC and psychomotor deficiency in kindergarteners, and we suggest that this may arise through critical stages of growth, not only via personal language communications, but psycho-social engagements as well. Therefore, a new hypothesis is proposed.

Experience of Early Childhood Caries May Positively Correlate with Psychomotor Development.

PURPOSE: To examine the as yet unknown relationship between dental caries and the child's psychomotor development. MATERIALS AND METHODS: A cross-sectional study was designed by screening the kindergartens from urban areas of two cities in southern Taiwan. Besides the personal, demographic and dietary information, the common measures for caries (dmft) and the amended comprehensive scales (CCDI) for psychomotor development were used to assess their relationship(s). A power analysis showed that 334 subjects would be required. One-way ANOVA vs multiple linear regression analysis were used to compare the differences of variables between gender, age and dmft scales, vs the relationship among all variables tested, respectively. RESULTS: A total of 433 children completed the study. The results demonstrated that there was a positive relationship between higher (i.e. dmft≥4 and 5) but not lower or extremely high caries experience and aspects of psychomotor development (i.e. personal-social and expressive language) in children aged 4 to 6 years. CONCLUSION: The present results are important for paediatric dentists, as they suggest a positive correlation between caries experience (dmft 3 to 6) and psychomotor development in pre-school children and that such a correlation may occur more significantly as an attribute of the most affected teeth (incisors and molars) during the critical stage of personal-social and expressive language development (speech-communication).