Scoping Review of Oral Health-Related Birth Cohort Studies: Toward a Global Consortium

The multidisciplinary nature and long duration of birth cohort studies allow investigation of the relationship between general and oral health and indicate the most appropriate stages in life to intervene. To date, the worldwide distribution of oral health-related birth cohort studies (OHRBCSs) has not been mapped, and a synthesis of information on methodological characteristics and outcomes is not available. We mapped published literature on OHRBCSs, describing their oral health-related data and methodological aspects. A 3-step search strategy was adopted to identify published studies using PubMed, Embase, Web of Science, and OVID databases. Studies with baseline data collection during pregnancy or within the first year of life or linked future oral health data to exposures during either of these 2 life stages were included. Studies examining only mothers' oral health and specific populations were excluded. In total, 1,721 articles were suitable for initial screening of titles and abstracts, and 528 articles were included in the review, identifying 120 unique OHRBCSs from 34 countries in all continents. The review comprised literature from the mid-1940s to the 21st century. Fifty-four percent of the OHRBCSs started from 2000 onward, and 75% of the cohorts were from high-income and only 2 from low-income countries. The participation rate between the baseline and the last oral health follow-up varied between 7% and 93%. Ten cohorts that included interventions were mostly from 2000 and with fewer than 1,000 participants. Seven data-linkage cohorts focused mostly on upstream characteristics and biological aspects. The most frequent clinical assessment was dental caries, widely presented as decayed, missing, and filled teeth (DMFT/dmft). Periodontal conditions were primarily applied as isolated outcomes or as part of a classification system. Socioeconomic classification, ethnicity, and country- or language-specific assessment tools varied across countries. Harmonizing definitions will allow combining data from different studies, adding considerable strength to data analyses; this will be facilitated by forming a global consortium.

Triacrylamide-Based Adhesives Stabilize Bonds in Physiologic Conditions

In this study, an acrylamide-based adhesive was combined with a thiourethane-based composite to improve bond stability and reduce polymerization stress, respectively, of simulated composite restorations. The stability testing was conducted under physiologic conditions, combining mechanical and bacterial challenges. Urethane dimethacrylate was combined with a newly synthesized triacrylamide (TMAAEA) or HEMA (2-hydroxyethyl-methacrylate; control) to produce a 2-step total-etch adhesive system. Methacrylate-based composites (70 wt% silanized filler) were formulated, containing thiourethane oligomers at 0 (control) or 20 wt%. Standardized preparations in human third molars were restored; then, epoxy replicas were obtained from the occlusal surfaces before and after 7-d storage in water or with Streptococcus mutans biofilm, which was tested after storage in an incubator (static) or the bioreactor (mechanical challenge). Images were obtained from the replicas (scanning electron microscopy) and cross sections of the samples (confocal laser scanning microscopy) and then analyzed to obtain measurements of gap, bacterial infiltration, and demineralization. Microtensile bond strength of specimens stored in water or biofilm was assessed in 1-mm2 stick specimens. Data were analyzed with analysis of variance and Tukey’s test (α = 0.05). HEMA-based materials had greater initial gap measurements, indicating more efficient bonding for the acrylamide materials. When tested in water, the triacrylamide-based adhesive had smaller gaps in the incubator or bioreactor. In the presence of biofilm, there was less difference among materials, but the acrylamide/thiourethane combination led to statistically lower gap formation in the bioreactor. HEMA and TMAAEA-based adhesives produced statistically similar microtensile bond strengths after being stored in water for 7 d, but after the same period with biofilm-challenged specimens, the TMAAEA-based adhesives were the only ones to retain the initial bond strength values. The use of a stable multiacrylamide-based adhesive led to the preservation of the resin-dentin bonded interface after a physiologically relevant challenge. Future studies will include a multispecies biofilm model.

Axin2+ PDL Cells Directly Contribute to New Alveolar Bone Formation in Response to Orthodontic Tension Force

Wnt–β-catenin signaling plays a key role in orthodontic tooth movement (OTM), a common clinical practice for malocclusion correction. However, its targeted periodontal ligament (PDL) progenitor cells remain largely unclear. In this study, we first showed a synchronized increase in Wnt–β-catenin levels and Axin2+ PDL progenitor cell numbers during OTM using immunostaining of β-catenin in wild-type mice and X-gal staining in the Axin2-LacZ knock-in line. Next, we demonstrated time-dependent increases in Axin2+ PDL progenitors and their progeny cell numbers within PDL and alveolar bones during OTM using a one-time tamoxifen-induced Axin2 tracing line ( Axin2CreERT2/+; R26RtdTomato/+). Coimmunostaining images displayed both early and late bone markers (such as RUNX2 and DMP1) in the Axin2Lin PDL cells. Conversely, ablation of Axin2+ PDL cells via one-time tamoxifen-induced diphtheria toxin subunit A (DTA) led to a drastic decrease in osteogenic activity (as reflected by alkaline phosphatase) in PDL and alveolar bone. There was also a decrease in new bone mass and a significant reduction in the mineral apposition rate on both the control side (to a moderate degree) and the OTM side (to a severe degree). Thus, we conclude that the Axin2+ PDL cells (the Wnt-targeted key cells) are highly sensitive to orthodontic tension force and play a critical role in OTM-induced PDL expansion and alveolar bone formation. Future drug development targeting the Axin2+ PDL progenitor cells may accelerate alveolar bone formation during orthodontic treatment.

Retinoic Acid Deficiency Underlies the Etiology of Midfacial Defects

Embryonic craniofacial development depends on the coordinated outgrowth and fusion of multiple facial primordia, which are populated with cranial neural crest cells and covered by the facial ectoderm. Any disturbance in these developmental events, their progenitor tissues, or signaling pathways can result in craniofacial deformities such as orofacial clefts, which are among the most common birth defects in humans. In the present study, we show that Rdh10 loss of function leads to a substantial reduction in retinoic acid (RA) signaling in the developing frontonasal process during early embryogenesis, which results in a variety of craniofacial anomalies, including midfacial cleft and ectopic chondrogenic nodules. Elevated apoptosis and perturbed cell proliferation in postmigratory cranial neural crest cells and a substantial reduction in Alx1 and Alx3 transcription in the developing frontonasal process were associated with midfacial cleft in Rdh10-deficient mice. More important, expanded Shh signaling in the ventral forebrain, as well as partial abrogation of midfacial defects in Rdh10 mutants via inhibition of Hh signaling, indicates that misregulation of Shh signaling underlies the pathogenesis of reduced RA signaling-associated midfacial defects. Taken together, these data illustrate the precise spatiotemporal function of Rdh10 and RA signaling during early embryogenesis and their importance in orchestrating molecular and cellular events essential for normal midfacial development.