Raman imaging demonstrates FGF2-induced craniosynostosis in mouse calvaria.
Craniosynostosis is a severe craniofacial disease where one or more sutures, the fibrous tissue that lies between the cranial bones, fuses prematurely. Some craniosynostosis syndromes are known to be caused by mutations in fibroblast growth factor (FGF) receptors. Mutated FGF receptors are thought to cause constitutive signaling. In this study, heparin acrylic beads released fibroblast growth factor 2 (FGF2) to mimic constitutive signaling by mutated receptors, delivering FGF2 in addition to already existing normal tissue amounts. Fetal day 18.5 mouse sutures were treated with FGF2-soaked beads and cultured in serum free media for 48 h. We have shown previously that this treatment leads to fusion and increased Msx2 expression, but here we use near-infrared Raman imaging to simultaneously examine the mineral components and matrix components of cranial tissue while providing light microscopic spatial information. FGF2-treated mouse sutures show increased v1 phosphate and v1 carbonate bandwidths, indicating a slightly chemically modified mineral being rapidly deposited. In addition, FGF2-treated mouse sutures show a marked increase in mineral-to-matrix ratios compared to control mouse sutures, typical of increased mineralization.
Crane
Nicole J
NJ
The University of Michigan, Department of Chemistry, Ann Arbor, Michigan 48109-1055, USA.
Morris
Michael D
MD
Ignelzi
Michael A
MA
Yu
Genggeng
G
D000465:Algorithms; D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D003398:Craniosynostoses / Q000139:chemically induced* / Q000175:diagnosis*; D016222:Fibroblast Growth Factor 2 / Q000009:adverse effects*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D051379:Mice; D012886:Skull / Q000187:drug effects* / Q000473:pathology*; D013059:Spectrum Analysis, Raman / Q000379:methods*
D016222:Fibroblast Growth Factor 2