title: Equibiaxial tensile strain affects calvarial osteoblast biology.
abstract: Mechanical tensile strain is believed to play an important role in regulating calvarial morphogenesis. To better understand the effects of mechanical strain on pathologic calvarial growth, we applied 10% constant equibiaxial tensile strain to neonatal rat calvarial osteoblast cultures and examined cellular proliferation, cytokine production, and extracellular matrix molecule expression. Mechanical strain markedly increased osteoblast proliferation as demonstrated by increased proliferating cell nuclear antigen (PCNA) protein. In addition, both transforming growth factor-beta1 (TGF-beta1) mRNA expression and fibroblast growth factor-2 (FGF-2) protein production were increased with exposure to strain. Moreover, mechanical strain induced expression of the extracellular matrix molecule collagen IalphaI. To further explore the relationship between mechanotransduction, osteogenesis, and angiogenesis, we examined the effect of mechanical strain on calvarial osteoblast expression of vascular endothelial growth factor (VEGF). Interestingly, we found that mechanical strain induced a rapid (within 3 hrs) increase in osteoblast VEGF expression. These data suggest that constant equibiaxial tensile strain-induced mechanotransduction can influence osteoblasts to assume an "osteogenic" and "angiogenic" phenotype, and these findings may have important implications for understanding the mechanisms of pathologic strain-induced calvarial growth.
authors.affiliation: Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA 94305-5148, USA.
authors.forename: Kenton D
authors.initials: KD
authors.lastname: Fong
authors.forename: Randall P
authors.initials: RP
authors.lastname: Nacamuli
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Loboa
authors.forename: James H
authors.initials: JH
authors.lastname: Henderson
authors.forename: Tony D
authors.initials: TD
authors.lastname: Fang
authors.forename: Hanjoon M
authors.initials: HM
authors.lastname: Song
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Cowan
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Warren
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Carter
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D016228:Endothelial Growth Factors / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D015870:Gene Expression; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism*; D009024:Morphogenesis; D010006:Osteoblasts / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000166:cytology / Q000254:growth & development*; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D024042:Collagen Type I; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D018809:Proliferating Cell Nuclear Antigen; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2