Impaired posterior frontal sutural fusion in the biglycan/decorin double deficient mice.
Biglycan (Bgn) and decorin (Dcn) are highly expressed in numerous tissues in the craniofacial complex. However, their expression and function in the cranial sutures are unknown. In order to study this, we first examined the expression of biglycan and decorin in the posterior frontal suture (PFS), which predictably fuses between 21 and 45 days post-natal and in the non-fusing sagittal (S) suture from wild-type (Wt) mice. Our data showed that Bgn and Dcn were expressed in both cranial sutures. We then characterized the cranial suture phenotype in Bgn deficient, Dcn deficient, Bgn/Dcn double deficient, and Wt mice. At embryonic day 18.5, alizarin red/alcian blue staining showed that the Bgn/Dcn double deficient mice had hypomineralization of the frontal and parietal craniofacial bones. Histological analysis of adult mice (45-60 days post-natal) showed that the Bgn or Dcn deficient mice had no cranial suture abnormalities and immunohistochemistry staining showed increased production of Dcn in the PFS from Bgn deficient mice. To test possible compensation of Dcn in the Bgn deficient sutures, we examined the Bgn/Dcn double deficient mice and found that they had impaired fusion of the PFS. Semi-quantitative RT-PCR analysis of RNA from 35 day-old mice revealed increased expression of Bmp-4 and Dlx-5 in the PFS compared to their non-fusing S suture in Wt tissues and decreased expression of Dlx-5 in both PF and S sutures in the Bgn/Dcn double deficient mice compared to the Wt mice. Failure of PFS fusion and hypomineralization of the calvaria in the Bgn/Dcn double deficient mice demonstrates that these extracellular matrix proteoglycans could have a role in controlling the formation and growth of the cranial vault.
Wadhwa
Sunil
S
Division of Orthodontics, School of Dental Medicine, Department of Craniofacial Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA. Wadhwa@uchc.edu
Bi
Yanming
Y
Ortiz
Ana T
AT
Embree
Mildred C
MC
Kilts
Tina
T
Iozzo
Renato
R
Opperman
Lynne A
LA
Young
Marian F
MF
D000423:Alcian Blue; D000818:Animals; D000880:Anthraquinones; D058578:Biglycan; D003393:Cranial Sutures / Q000002:abnormalities* / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011247:Pregnancy; D011509:Proteoglycans / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling
D000880:Anthraquinones; C546885:Bgn protein, mouse; D058578:Biglycan; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; C010078:alizarin; D000423:Alcian Blue