title: Fluid shear of low magnitude increases growth and expression of TGFbeta1 and adhesion molecules in human bone cells in vitro.
abstract: Deformation of the bone matrix by mechanical strain causes fluid shifts within the osteocytic canaliculi which affect osteocytic cell metabolism. We applied low fluid shear (1 - 63 micro Pa for 10 - 48 h) to human osteoblastic cells (HOB) in vitro to study its impact on cell proliferation and differentiated functions. Proteins involved in translating the physical force into a cellular response were characterised. Low fluid shear stress stimulated proliferation of HOB 1.2-fold when stress was applied intermittently for 24 h. Shear stress also increased differentiated cellular properties such as alkaline phosphatase (ALP) activity (121 % of control), fibronectin (FN) and fibronectin receptor (FNR) expression (290 % and 200 %, respectively). Prostaglandin E (2) (PGE (2)) and TGFbeta1 release into the medium were significantly stimulated when shear stress was applied for 6 - 12 h and 24 - 48 h, respectively. TGFbeta1 + 2 neutralising antibodies or the presence of indomethacine inhibited the mitogenic effect of fluid shear and reduced ALP activity to its control level. Furthermore, TGFbeta treatment induced a dose-dependent increase in FN and FNR expression. Therefore, fluid shear stress of low magnitude (a) suffices to affect HOB metabolism and (b) regulates anchorage of HOB via FN and FNR by stimulating osteoblastic PGE (2) and TGFbeta secretion.
authors.affiliation: Endocrinology and Metabolism, Department of Medicine, Ruprecht-Karls-University, Heidelberg, Germany.
authors.forename: U M
authors.initials: UM
authors.lastname: Liegibel
authors.forename: U
authors.initials: U
authors.lastname: Sommer
authors.forename: B
authors.initials: B
authors.lastname: Bundschuh
authors.forename: B
authors.initials: B
authors.lastname: Schweizer
authors.forename: U
authors.initials: U
authors.lastname: Hilscher
authors.forename: A
authors.initials: A
authors.lastname: Lieder
authors.forename: P
authors.initials: P
authors.lastname: Nawroth
authors.forename: C
authors.initials: C
authors.lastname: Kasperk
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D005353:Fibronectins / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D039081:Integrin alpha5beta1 / Q000032:analysis / Q000096:biosynthesis; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology*; D012212:Rheology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2
chemical_list: D000906:Antibodies; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D039081:Integrin alpha5beta1; C508960:TGFB1 protein, human; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D000469:Alkaline Phosphatase; D015232:Dinoprostone