Biglycan and Decorin: Potential Role in Controlling Suture Maturation and Craniofacial Development

Biglycan (BGN) and decorin (DCN) are members of a family of proteins known as SLRPs (Small leucine rich proteoglycans). They are abundantly expressed in the craniofacial complex and are believed to have similar physiologic roles important for growth factor binding and function. Thus, the absence of one SLRP may be compensated by the presence of another. Objective: Determine whether BGN and DCN play a role in craniofacial development by characterizing the phenotype of mice deficient in both small proteoglycans. Methods: BGN and DCN (KO) mice were generated by breeding single KO’s to each other. Normal (Wildtype=WT) and mutant mice were sacrificed at sixty days (N=4) and skulls were analyzed by micro CT and by faxitron X-ray using multiple views. Calvariae were dissected free from skull for isolated X-ray analysis, to obtain clearer views of suture morphology. A visual analogue scale was created to evaluate the extent of sutural closing. Results: The skulls from the BGN/DCN KO mice were 40% smaller in the anterior posterior direction compared to WT while the transverse and vertical dimension appeared unaffected. In normal mice, the posterior frontal suture normally fuses within 25-45 days after birth. Analysis of experimental 60 day-old mice showed the posterior frontal sutures in the BGN/DCN KO were only 8% +/-3% fused compared to the wildtype mice which was 95% +/- 10% fused. In addition, the frontal suture in the BGN/DCN KO had an abnormal shape and lacked symmetry compared to WT controls. Conclusion: The absence of BGN and DCN causes foreshortened skulls, which may be due to abnormal sutural growth in the craniofacial complex. The data also imply that BGN and DCN could be involved in human conditions caused by abnormal sutural morphology such as enlarged parietal foramina.