TY - JOUR
T1 - Cranial bone microarchitecture in a mouse model for syndromic craniosynostosis
AU - Ajami, Sara
AU - Van den Dam, Zoe
AU - Hut, Julia
AU - Savery, Dawn
AU - Chin, Milton
AU - Koudstaal, Maarten
AU - Steacy, Miranda
AU - Carriero, Alessandra
AU - Pitsillides, Andrew
AU - Chang, Y. -m.
AU - Rau, Christoph
AU - Marathe, Shashidhara
AU - Dunaway, David
AU - Jeelani, Noor Ul Owase
AU - Schievano, Silvia
AU - Pauws, Erwin
AU - Borghi, Alessandro
N1 - Publisher Copyright:
© 2024 The Author(s). Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.
PY - 2024/8/2
Y1 - 2024/8/2
N2 - 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 FGFR2
C342Y 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 FGFR2
C342Y/+ (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.
AB - 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 FGFR2
C342Y 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 FGFR2
C342Y/+ (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.
UR - http://www.scopus.com/inward/record.url?scp=85200237575&partnerID=8YFLogxK
U2 - 10.1111/joa.14121
DO - 10.1111/joa.14121
M3 - Article
C2 - 39096036
SN - 0021-8782
VL - 245
SP - 864
EP - 873
JO - Journal of Anatomy
JF - Journal of Anatomy
IS - 6
ER -