Preface to the 9th Biennial COAST Conference: Harnessing Technology and Biomedicine for Personalized Orthodontics.

OBJECTIVE: The Consortium on Orthodontic Advances in Science and Technology (COAST) convened for its 9th biennial conference titled 'Harnessing Technology and Biomedicine for Personalized Orthodontics' to explore cutting-edge craniofacial research towards building the foundations for precision care in orthodontics. SETTING AND SAMPLE POPULATION: Seventy-five faculty, scholars, private practitioners, industry, residents and students met at the UCLA Arrowhead Lodge on 6-9 November 2022 for networking, scientific presentations and facilitated discussions. Thirty-three speakers provided state-of-the-art, evidence-based scientific and perspective updates in craniofacial and orthodontic-related fields. The overall format included an Education Innovation Award Faculty Development Career Enrichment (FaCE) workshop focused on faculty career development, three lunch and learns, keynote or short talks and poster presentations. MATERIAL AND METHODS: The 2022 COAST Conference was organized thematically to include (a) genes, cells and environment in craniofacial development and abnormalities; (b) precision modulation of tooth movement, retention and facial growth; (c) applications of artificial intelligence in craniofacial health; (d) precision approaches to Sleep Medicine, OSA and TMJ therapies; and (e) precision technologies and appliances. RESULTS: The collective advances in orthodontics and science represented in the manuscripts of this issue fulfil our goal of laying solid foundations for personalized orthodontics. Participants elevated the need for stronger industry-academic research partnerships to leverage knowledge gained from large datasets with treatment approaches and outcomes; systematizing the potential of big data including through multi-omics and artificial intelligence approaches; refining the genotype: phenotype correlation to create biotechnology that will rescue inherited dental and craniofacial defects; evolving studies of tooth movement, sleep apnoea and TMD treatment to accurately measure dysfunction and treatment successes; and maximizing the integration of newer orthodontic devices and digital workflows. CONCLUSIONS: Technological advances combined with those in biomedicine and machine learning are rapidly changing the delivery of health care including that in orthodontics. These advances promise to lead to enhanced customization, efficiencies and outcomes of patient care in routine orthodontic problems and in severe craniofacial problems, OSA and TMD.

Mouse models for the study of cranial base growth and anomalies.

The cranial base is a central and integral component of the cranioskeleton, yet little is known about its growth. Despite the dissimilarities between human and murine cranioskeletal form, mouse models are proving instrumental in studying craniofacial growth. The objectives of this review are to summarize recent findings from numerous mouse models that display growth defects in one or more cranial base synchondroses, with accompanying changes in chondrocyte cellular zones. Many of these models also display altered growth of the cranial vault and/or the facial region. FGFR, PTHrP, Ihh, BMP and Wnt/ß-catenin, as well as components of primary cilia, are the major genes and signalling pathways identified in cranial base synchondroses. Together, these models are helping to uncover specific genetic influences and signalling pathways operational at the cranial base synchondroses. Many of these genes are in common with those of importance in the cranial vault and the facial skeleton, emphasizing the molecular integration of growth between the cranial base and other cranial regions. Selected models are also being utilized in testing therapeutic agents to correct defective craniofacial and cranial base growth.

Global strain field mapping of a particle-laden interface using digital image correlation.

HYPOTHESIS: The ability to identify the stress-strain relations correctly is critical to understanding and modeling any rheological responses of an interface. Langmuir-Pockels (LP) trough is one of the most commonly used tools for studying an interface. Most, if not all, existing studies assume a 1D uniaxial compression during a LP-trough compression experiment. It is hypothesized that the deformation field is far more complex than what is typically assumed. EXPERIMENTS: To examine this hypothesis, we custom-built a glass-bottomed LP trough equipped with a camera to capture a series of optical images asa carbon nanotube (CNT)-laden interface is compressed. A digital image correlation (DIC) technique was then applied to the images to evaluate the global strain field during compression of the CNT laden interface. The DIC-corrected strain data were subsequently analyzed with the surface stress data to quantify the surface shear and dilatational moduli of the CNT-laden interface. FINDINGS: Our experimental findings clearly show, for the first time, the development of a non-uniform and complex 2D strain field during compression. The local strains were further quantified and compared with the usual assumption of 1D uniaxial compression. Although the compressive strain averaged over the whole trough area closely resembles the 1D uniaxial compression strain, the 1D compression assumption underestimates the local strain by about 36% at the center of the trough, where the surface stresses are measured. This is the first study in applying the DIC technique to map out the global strain field asa particle-laden interface is compressed. The method may also be applicable to other systems with similar optical texture, allowing the correct identification of stress-strain relationship of an interface.

Automated Detection of 3D Landmarks for the Elimination of Non-Biological Variation in Geometric Morphometric Analyses.

Landmark-based morphometric analyses are used by anthropologists, developmental and evolutionary biologists to understand shape and size differences (eg. in the cranioskeleton) between groups of specimens. The standard, labor intensive approach is for researchers to manually place landmarks on 3D image datasets. As landmark recognition is subject to inaccuracies of human perception, digitization of landmark coordinates is typically repeated (often by more than one person) and the mean coordinates are used. In an attempt to improve efficiency and reproducibility between researchers, we have developed an algorithm to locate landmarks on CT mouse hemi-mandible data. The method is evaluated on 3D meshes of 28-day old mice, and results compared to landmarks manually identified by experts. Quantitative shape comparison between two inbred mouse strains demonstrate that data obtained using our algorithm also has enhanced statistical power when compared to data obtained by manual landmarking.

Lysyl oxidase propeptide inhibits prostate cancer cell growth by mechanisms that target FGF-2-cell binding and signaling.

Enhanced RAS signaling and decreased androgen dependence of prostate cancer cells accompany poor clinical outcomes. Elevated autocrine fibroblast growth factors 2 (FGF-2) signaling promotes prostate cancer cell growth and survival. Expression of lysyl oxidase (LOX) inhibits RAS transforming activity. LOX is secreted as 50 kDa pro-LOX protein and then undergoes extracellular proteolytic processing to form approximately 30 kDa LOX enzyme and approximately 18 kDa propeptide (LOX-PP). We have previously shown that LOX-PP inhibits breast cancer cell transformation and tumor formation, but mechanisms of action of LOX-PP have not been fully elucidated. Here we report that LOX expression is reduced in prostate cancer cell lines and that recombinant LOX-PP protein inhibits serum-stimulated DNA synthesis and MEK/ERK and PI3K/AKT pathways in DU 145 and PC-3 androgen-independent cell lines. In DU 145 cells, treatment with a pharmacologic FGF-receptor inhibitor or a neutralizing anti-FGFR1 antibody mimicked LOX-PP inhibition of serum-stimulated DNA synthesis. FGF-2-stimulated DNA synthesis, ERK1/2, AKT and FRS2alpha activation were found all to be inhibited by LOX-PP in DU 145 cells. LOX-PP reduced specific binding of FGF-2 to DU 145 cells, suggesting that LOX-PP targets FGF signaling at the receptor. Interestingly, PC-3 cells did not respond to FGF-2, consistent with previous reports. We conclude that LOX-PP inhibits proliferation of DU 145 cells by interfering with FGFR(s) binding and signaling, and that LOX-PP has other mechanisms of action in PC-3 cells.