title: Differential spatial regulation of BMP molecules is associated with single-suture craniosynostosis.
abstract: OBJECTIVE The aim of this study was to examine messenger RNA (mRNA) levels of bone morphogenetic protein (BMP) ligands, receptors, and soluble inhibitors in cells isolated from single-suture synostoses from fused coronal, metopic, sagittal, and lambdoid sutures. METHODS Cells were isolated from bone collected from patients undergoing craniotomies at Children's Healthcare of Atlanta. Real-time polymerase chain reaction was used to examine mRNA levels in cells isolated from fused sutures or patent sutures in comparison with levels in normal bone from the same patient. RESULTS Cells isolated from fused sutures in cases of sagittal and coronal synostosis highly expressed BMP2, while cells isolated from fused metopic or lambdoid synostosis expressed high BMP4. Noggin, a BMP inhibitor, was lower in fused sutures and had high expression in patent sutures. CONCLUSIONS These results suggest that BMPs and inhibitors play a significant role in the regulation of suture fusion as well in the maintenance of patency in the normal suture.
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, Georgia;
authors.forename: Alaina
authors.initials: A
authors.lastname: Whitton
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia;
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Hyzy
authors.affiliation: Medical College of Georgia, Georgia Regents University, Augusta, Georgia;
authors.forename: Chelsea
authors.initials: C
authors.lastname: Britt
authors.affiliation: Children's Healthcare of Atlanta, Georgia; and.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Williams
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia;|Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia.
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Boyan
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia;
authors.forename: Rene
authors.initials: R
authors.lastname: Olivares-Navarrete
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis*; D055415:Bone Morphogenetic Protein 4 / Q000096:biosynthesis*; D002478:Cells, Cultured; D015331:Cohort Studies; D003393:Cranial Sutures / Q000166:cytology / Q000378:metabolism*; D003398:Craniosynostoses / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: C525718:BMP2 protein, human; C525809:BMP4 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D012333:RNA, Messenger
keywords: BMP = bone morphogenetic protein; CHOA = Children's Healthcare of Atlanta; FGF = fibroblast growth factor; GAPDH = glyceraldehyde 3-phosphate dehydrogenase; PCR = polymerase chain reaction; bone; bone morphogenetic protein; cDNA = complementary DNA; cranial sutures; craniofacial; craniosynostosis; mRNA = messenger RNA; qPCR = quantitative PCR