Cranial bone microarchitecture in a mouse model for syndromic craniosynostosis

Ajami, Sara; Van den Dam, Zoe; Hut, Julia; Savery, Dawn; Chin, Milton; Koudstaal, Maarten; Steacy, Miranda; Carriero, Alessandra; Pitsillides, Andrew; Chang, Y.‐M.; Rau, Christoph; Marathe, Shashidhara; Dunaway, David; Jeelani, Noor Ul Owase; Schievano, Silvia; Pauws, Erwin; Borghi, Alessandro

Abstract

Crouzon syndrome is a congenital craniofacial disorder caused by mutations in the Fibroblast Growth Factor Receptor 2 (FGFR2). It is characterized by the premature fusion of cranial sutures, leading to a brachycephalic head shape, and midfacial hypoplasia. The aim of this study was to investigate the effect of the FGFR2 mutation on the microarchitecture of cranial bones at different stages of postnatal skull development, using the FGFR2C342Y mouse model. Apart from craniosynostosis, this model shows cranial bone abnormalities. High‐resolution synchrotron microtomography images of the frontal and parietal bone were acquired for both FGFR2C342Y/+ (Crouzon, heterozygous mutant) and FGFR2+/+ (control, wild‐type) mice at five ages (postnatal days 1, 3, 7, 14 and 21, n = 6 each). Morphometric measurements were determined for cortical bone porosity: osteocyte lacunae and canals. General linear model to assess the effect of age, anatomical location and genotype was carried out for each morphometric measurement. Histological analysis was performed to validate the findings. In both groups (Crouzon and wild‐type), statistical difference in bone volume fraction, average canal volume, lacunar number density, lacunar volume density and canal volume density was found at most age points, with the frontal bone generally showing higher porosity and fewer lacunae. Frontal bone showed differences between the Crouzon and wild‐type groups in terms of lacunar morphometry (average lacunar volume, lacunar number density and lacunar volume density) with larger, less dense lacunae around the postnatal age of P7–P14. Histological analysis of bone showed marked differences in frontal bone only. These findings provide a better understanding of the pathogenesis of Crouzon syndrome and will contribute to computational models that predict postoperative changes with the aim to improve surgical outcome.

Citation

Ajami, S., Van den Dam, Z., Hut, J., Savery, D., Chin, M., Koudstaal, M., Steacy, M., Carriero, A., Pitsillides, A., Chang, Y., Rau, C., Marathe, S., Dunaway, D., Jeelani, N. U. O., Schievano, S., Pauws, E., & Borghi, A. (online). Cranial bone microarchitecture in a mouse model for syndromic craniosynostosis. Journal of Anatomy, https://doi.org/10.1111/joa.14121

• Journal Article Type: Article
• Acceptance Date: Jul 23, 2024
• Online Publication Date: Aug 2, 2024
• Deposit Date: Aug 13, 2024
• Publicly Available Date: Aug 13, 2024
• Journal: Journal of Anatomy
• Print ISSN: 0021-8782
• Electronic ISSN: 1469-7580
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1111/joa.14121
• Keywords: Crouzon, FGFR2, craniosynostosis, bone, craniofacial
• Public URL: https://durham-repository.worktribe.com/output/2748722