title: Proliferation, osteogenic differentiation, and fgf-2 modulation of posterofrontal/sagittal suture-derived mesenchymal cells in vitro.
abstract: BACKGROUND
  Fibroblast growth factor (FGF) signaling is of central importance in premature cranial suture fusion. In the murine skull, the posterofrontal suture normally fuses in early postnatal life, whereas the adjacent sagittal suture remains patent. The authors used a recently developed isolation technique for in vitro culture of suture-derived mesenchymal cells to examine the effects of FGF-2 on proliferation and differentiation of posterofrontal and sagittal suture-derived mesenchymal cells.
  
  
  METHODS
  Skulls were harvested from 40 mice (5-day-old). Posterofrontal and sagittal sutures were dissected, separating sutural mesenchymal tissue from dura mater and pericranium, and cultured. After cell migration from the explant and subculture, differences in proliferation and osteogenic differentiation of these distinct populations were studied. The mitogenic and osteogenic effects of recombinant FGF-2 were then assessed. FGF-2 regulation of gene expression was evaluated.
  
  
  RESULTS
  Suture-derived mesenchymal cells isolated from the posterofrontal suture demonstrated significantly higher proliferation rates and a robust mitogenic response to FGF-2 as compared with suture-derived mesenchymal cells isolated from the sagittal suture. Interestingly, posterofrontal suture-derived mesenchymal cells retained a higher in vitro osteogenic potential, as shown by alkaline phosphatase activity and bone nodule formation. FGF-2 significantly diminished osteogenesis in both suture-derived mesenchymal cell populations. Subsequently, Ob-cadherin and Sox9 were found to be differentially expressed in posterofrontal versus sagittal suture-derived mesenchymal cells and dynamically regulated by FGF-2.
  
  
  CONCLUSIONS
  In vitro osteogenesis of suture-derived mesenchymal cells recapitulates in vivo posterofrontal and sagittal sutural fates. Posterofrontal rather than sagittal suture-derived mesenchymal cells are more responsive to FGF-2 in vitro, in terms of both mitogenesis and osteogenesis.
authors.affiliation: Stanford, Calif. From the Hagey Pediatric Regenerative Medicine Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine.
authors.forename: Aaron W
authors.initials: AW
authors.lastname: James
authors.forename: Yue
authors.initials: Y
authors.lastname: Xu
authors.forename: Ruidi
authors.initials: R
authors.lastname: Wang
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003393:Cranial Sutures / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D051379:Mice; D023421:Models, Animal; D010012:Osteogenesis / Q000187:drug effects
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D016222:Fibroblast Growth Factor 2