Craniofacial Bone Mineral Density in Mice with Osteogenesis Imperfecta (OI)

Abstract

Osteogenesis Imperfecta (OI) is a rare genetic disorder characterized by a point mutation in COL1A1 or COL1A2 genes that leads to the abnormal synthesis and assembly of type I collagen, a major organic component of bone. Clinical manifestations of the severe OI Type III include small body size, limb deformities, and low bone mineral density (BMD) within the post‐cranial skeleton. OI type III often co‐occurs with dentinogenesis imperfecta (DI), especially in juveniles. The goals of this study are: (1) to investigate the relationship between the organic and inorganic components of bone in the craniofacial skeleton; and (2) to examine whether an abnormality in type I collagen, as seen in OI, affects BMD within the craniofacial skeleton.The homozygous recessive murine mouse (OIM−/−) is a model for OI Type III. Similar to human OI patients, OIM−/− mice exhibit low BMD within post‐cranial elements such as the femur, smaller body size, and DI. OIM−/− mice and WT littermates were weaned at 21 days and CT scans were performed longitudinally at 4 weeks, 10 weeks, and 16 weeks of age. BMD at three regions of interest (ROIs) within the mandible were measured using Bruker CT Analyzer software. ROIs were selected on the basis of high vs. low loading during mastication, and included the temporomandibular joint (TMJ), buccal side of the mandibular corpus at the level of the second molar (M2), and the mandibular symphysis. Kruskal‐Wallis ANOVAs were used to statistically compare BMD between genotypes (α = 0.05). Adult OIM−/− mice (n=6) have significantly lower BMD within the mandibular corpus near M2 as compared to WT mice (n=6). Differences in BMD means between OIM−/− and WT mice were not significant at the TMJ or the mandibular symphysis. Future studies will quantify BMD at additional ROIs within the craniofacial skeleton, and following the ontogenetic trajectory of BMD in the craniofacial skeleton from weaning to adulthood.Support or Funding InformationThis research was supported by an Indiana University Collaborative Research Grant and the Ralph W. and Grace Showalter Trust.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.