Cranial bone microarchitecture in a mouse model for syndromic craniosynostosis

Area of Science:

• Craniofacial Development and Genetics
• Bone Biology and Histomorphometry
• Developmental Biology

Background:

• Crouzon syndrome is a genetic disorder characterized by premature cranial suture fusion and midfacial hypoplasia, stemming from Fibroblast Growth Factor Receptor 2 (FGFR2) mutations.
• The specific impact of FGFR2 mutations on the intricate microarchitecture of developing cranial bones remains incompletely understood.

Purpose of the Study:

• To investigate the effects of the FGFR2^C342Y mutation on cranial bone microarchitecture during postnatal development.
• To analyze changes in cortical bone porosity, specifically osteocyte lacunae and canals, in a mouse model of Crouzon syndrome.

Main Methods:

• Utilized high-resolution synchrotron microtomography to image frontal and parietal bones of FGFR2^C342Y/+ (Crouzon) and wild-type mice at five postnatal ages (P1, P3, P7, P14, P21).
• Performed morphometric measurements of cortical bone porosity, including osteocyte lacunae and canals.
• Employed general linear models to assess the influence of age, anatomical location, and genotype, with histological analysis for validation.

Main Results:

• Both Crouzon and wild-type mice exhibited age-related differences in bone volume fraction, canal volume, lacunar number density, and lacunar/canal volume densities.
• Frontal bone generally displayed higher porosity and fewer lacunae compared to parietal bone across both genotypes.
• Significant differences in frontal bone lacunar morphometry (larger, less dense lacunae) were observed in Crouzon mice around postnatal days 7-14.

Conclusions:

• FGFR2 mutations in Crouzon syndrome lead to distinct alterations in cranial bone microarchitecture, particularly affecting frontal bone lacunar morphology during early postnatal development.
• These findings enhance understanding of Crouzon syndrome pathogenesis.
• The results can inform computational models for predicting surgical outcomes in craniofacial reconstruction.