Browsing by Subject "Congenital cortical hyperostosis"

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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.