Browsing by Author "Helms, J. A."

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    Interspecies Comparison of Alveolar Bone Biology, Part I: Morphology and Physiology of Pristine Bone
    (Sage, 2021) Pilawski, I.; Tulu, U. S.; Ticha, P.; Schüpbach, P.; Traxler, H.; Xu, Q.; Pan, J.; Coyac, B. R.; Yuan, X.; Tian, Y.; Liu, Y.; Chen, J.; Erdogan, Y.; Arioka, M.; Armaro, M.; Wu, M.; Brunski, J. B.; Helms, J. A.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Introduction: Few interspecies comparisons of alveolar bone have been documented, and this knowledge gap raises questions about which animal models most accurately represent human dental conditions or responses to surgical interventions. Objectives: The objective of this study was to employ state-of-the-art quantitative metrics to directly assess and compare the structural and functional characteristics of alveolar bone among humans, mini pigs, rats, and mice. Methods: The same anatomic location (i.e., the posterior maxillae) was analyzed in all species via micro-computed tomographic imaging, followed by quantitative analyses, coupled with histology and immunohistochemistry. Bone remodeling was evaluated with alkaline phosphatase activity and tartrate-resistant acid phosphatase staining to identify osteoblast and osteoclast activities. In vivo fluorochrome labeling was used as a means to assess mineral apposition rates. Results: Collectively, these analyses demonstrated that bone volume differed among the species, while bone mineral density was equal. All species showed a similar density of alveolar osteocytes, with a highly conserved pattern of collagen organization. Collagen maturation was equal among mouse, rat, and mini pig. Bone remodeling was a shared feature among the species, with morphologically indistinguishable hemiosteonal appearances, osteocytic perilacunar remodeling, and similar mineral apposition rates in alveolar bone. Conclusions: Our analyses demonstrated equivalencies among the 4 species in a plurality of the biological features of alveolar bone. Despite contradictory results from older studies, we found no evidence for the superiority of pig models over rodent models in representing human bone biology. Knowledge transfer statement: Animal models are extensively used to evaluate bone tissue engineering strategies, yet there are few state-of-the-art studies that rigorously compare and quantify the factors influencing selection of a given animal model. Consequently, there is an urgent need to assess preclinical animal models for their predictive value to dental research. Our article addresses this knowledge gap and, in doing so, provides a foundation for more effective standardization among animal models commonly used in dentistry.
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    Wnt/β-catenin Signaling Controls Maxillofacial Hyperostosis
    (Sage, 2022) Chen, J.; Cuevas, P. L.; Dworan, J. S.; Dawid, I.; Turkkahraman, H.; Tran, K.; Delgado-Calle, J.; Bellido, T.; Gorski, J. P.; Liu, B.; Brunski, J. B.; Helms, J. A.; Orthodontics and Oral Facial Genetics, School of Dentistry
    The roles of Wnt/β-catenin signaling in regulating the morphology and microstructure of craniomaxillofacial (CMF) bones was explored using mice carrying a constitutively active form of β-catenin in activating Dmp1-expressing cells (e.g., daβcatOt mice). By postnatal day 24, daβcatOt mice exhibited midfacial truncations coupled with maxillary and mandibular hyperostosis that progressively worsened with age. Mechanistic insights into the basis for the hyperostotic facial phenotype were gained through molecular and cellular analyses, which revealed that constitutively activated β-catenin in Dmp1-expressing cells resulted in an increase in osteoblast number and an increased rate of mineral apposition. An increase in osteoblasts was accompanied by an increase in osteocytes, but they failed to mature. The resulting CMF bone matrix also had an abundance of osteoid, and in locations where compact lamellar bone typically forms, it was replaced by porous, woven bone. The hyperostotic facial phenotype was progressive. These findings identify for the first time a ligand-independent positive feedback loop whereby unrestrained Wnt/β-catenin signaling results in a CMF phenotype of progressive hyperostosis combined with architecturally abnormal, poorly mineralized matrix that is reminiscent of craniotubular disorders in humans.