Sara Ajami, Zoe Van den Dam, Julia Hut, Dawn Savery, Milton Chin, Maarten Koudstaal, Miranda Steacy, Alessandra Carriero, Andrew Pitsillides, Y-M Chang, Christoph Rau, Shashidhara Marathe, David Dunaway, Noor Ul Owase Jeelani, Silvia Schievano, Erwin Pauws, Alessandro Borghi
{"title":"综合征颅骨发育不良小鼠模型的颅骨微结构。","authors":"Sara Ajami, Zoe Van den Dam, Julia Hut, Dawn Savery, Milton Chin, Maarten Koudstaal, Miranda Steacy, Alessandra Carriero, Andrew Pitsillides, Y-M Chang, Christoph Rau, Shashidhara Marathe, David Dunaway, Noor Ul Owase Jeelani, Silvia Schievano, Erwin Pauws, Alessandro Borghi","doi":"10.1111/joa.14121","DOIUrl":null,"url":null,"abstract":"<p><p>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<sup>C342Y</sup> 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<sup>C342Y/+</sup> (Crouzon, heterozygous mutant) and FGFR2<sup>+/+</sup> (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.</p>","PeriodicalId":14971,"journal":{"name":"Journal of Anatomy","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cranial bone microarchitecture in a mouse model for syndromic craniosynostosis.\",\"authors\":\"Sara Ajami, Zoe Van den Dam, Julia Hut, Dawn Savery, Milton Chin, Maarten Koudstaal, Miranda Steacy, Alessandra Carriero, Andrew Pitsillides, Y-M Chang, Christoph Rau, Shashidhara Marathe, David Dunaway, Noor Ul Owase Jeelani, Silvia Schievano, Erwin Pauws, Alessandro Borghi\",\"doi\":\"10.1111/joa.14121\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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<sup>C342Y</sup> 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<sup>C342Y/+</sup> (Crouzon, heterozygous mutant) and FGFR2<sup>+/+</sup> (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.</p>\",\"PeriodicalId\":14971,\"journal\":{\"name\":\"Journal of Anatomy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2024-08-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Anatomy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/joa.14121\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ANATOMY & MORPHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Anatomy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/joa.14121","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}
Cranial bone microarchitecture in a mouse model for syndromic craniosynostosis.
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.
期刊介绍:
Journal of Anatomy is an international peer-reviewed journal sponsored by the Anatomical Society. The journal publishes original papers, invited review articles and book reviews. Its main focus is to understand anatomy through an analysis of structure, function, development and evolution. Priority will be given to studies of that clearly articulate their relevance to the anatomical community. Focal areas include: experimental studies, contributions based on molecular and cell biology and on the application of modern imaging techniques and papers with novel methods or synthetic perspective on an anatomical system.
Studies that are essentially descriptive anatomy are appropriate only if they communicate clearly a broader functional or evolutionary significance. You must clearly state the broader implications of your work in the abstract.
We particularly welcome submissions in the following areas:
Cell biology and tissue architecture
Comparative functional morphology
Developmental biology
Evolutionary developmental biology
Evolutionary morphology
Functional human anatomy
Integrative vertebrate paleontology
Methodological innovations in anatomical research
Musculoskeletal system
Neuroanatomy and neurodegeneration
Significant advances in anatomical education.