THE EFFECT OF BONE MORPHOGENETIC PROTEIN 2(BMP2) ON THE GROWTH OF CRANIAL BONE AND EARLY MORPHOGENESIS OF THE CRANIAL SUTURE

Bone Morphogenetic Protein 2 가 두개골 성장 및 두개봉합부의 초기형태발생에 미치는 영향

  • Jung, Hae-Kyung (Department of Pediatric Dentistry, College of Dentistry, Kyungpook National University) ;
  • Park, Mi-Hyun (Department of Oral Biochemistry, College of Dentistry, Kyungpook National University) ;
  • Ryoo, Hyun-Mo (Department of Oral Biochemistry, College of Dentistry, Kyungpook National University) ;
  • Nam, Soon-Hyeun (Department of Pediatric Dentistry, College of Dentistry, Kyungpook National University) ;
  • Kim, Young-Jin (Department of Pediatric Dentistry, College of Dentistry, Kyungpook National University) ;
  • Kim, Hyun-Jung (Department of Pediatric Dentistry, College of Dentistry, Kyungpook National University)
  • 정혜경 (경북대학교 소아치과학교실) ;
  • 박미현 (경북대학교 구강생화학교실) ;
  • 유현모 (경북대학교 구강생화학교실) ;
  • 남순현 (경북대학교 소아치과학교실) ;
  • 김영진 (경북대학교 소아치과학교실) ;
  • 김현정 (경북대학교 소아치과학교실)
  • Published : 2003.05.31

Abstract

Co-ordinate growth of the brain and skull is achieved through a series of tissue interactions between the developing brain, the growing bones of the skull and the sutures that unite the bones. Craniosynostosis, the premature fusion of cranial sutures, presumably involves disturbance of these interactions. Bmp2, one of bone morphogenetic proteins (Bmps), is involved in the regulation of the shapes of individual bones and the relative proportions of the skeleton. Mutations in the homeobox gene Msx2, known as a downstream gene of Bmp, cause Boston-type human craniosynostosis. The phenotype of Dlx5 homozygote mutant mouse presents craniofacial abnormalities including a delayed ossification of calvarial bone. These facts suggest important roles of Bmp2, Msx2 and Dlx5 genes in the cranial bone growth and suture morphogenesis. To elucidate the function of these molecules in the early morphogenesis of mouse cranial sutures, we first analyzed by in situ hybridization the expression of Bmp2(E15-18), Msx2 and Dlx5 genes in the developing sagittal suture of calvaria during the embryonic stage. Bmp2 mRNA was intensely expressed in the osteogenic fronts and also at the low level in the periosteum of parietal bones during embryonic stage, Msx2 mRNA was intensely expressed in the sutural mesenchyme and mildly expressed in the dura mater during the embryonic stage. Dlx5 mRNA was intensely expressed osteogenic fronts and parietal bones. To further examine the role of Bmp signaling in cranial suture, we did in vitro experiments in E15.5 mouse calvarial explants. Interestingly, implantation of Bmp2-soaked beads onto the osteogenic fronts after 48 hours organ culture resulted in the increase of the tissue thickness and cell number around Bmp2 beads, compared to BSA control beads. In addition Bmp2 induced etopic expressions of Msx2 and Dlx5 genes. On the other hand, overexpression of FGF2 did not induce the expression of Msx2 and Dlx5. Taken together, these data indicate that Bmp2 signaling molecule has a important role in regulating the cranial bone growth and early morphogenesis of cranial suture. We also suggest that Bmp signaling is involved in all the stages of osteogenesis of cranial bones and the maintenance of cranial suture by regulating Msx2 and Dlx5 genes, and that Msx2 and Dlx5 genes are specific transcription factors of Bmp signaling pathway.