title: Extracellular matrix regulates induction of alkaline phosphatase expression by ascorbic acid in human fibroblasts.
abstract: During wound healing and inflammation, fibroblasts express elevated alkaline phosphatase (ALP), but are not in contact with collagen fibrils in the fibronectin (FN)-rich granulation tissue. We hypothesized that the extracellular matrix (ECM) environment might influence the induction of ALP in fibroblasts. Here we tested this hypothesis by studying the ALP-inductive response of normal human gingival fibroblasts to ascorbic acid (AsA). AsA induced ALP activity and protein in cells in conventional monolayer culture. This induction was inhibited by blocking-antibodies to the FN receptor alpha 5 beta 1 integrin and by the proline analog 3,4-dehydroproline (DHP). DHP prevented cells from arranging FN fibrils into a pericellular network and reduced the activity of cell spreading on FN. Plating of cells on FN facilitated the up-regulation by AsA of ALP expression, but did not substitute for AsA. In contrast, AsA did not cause ALP induction in cells cultured on and in polymerized type I collagen gels. Collagen fibrils inhibited the up-regulation by AsA of ALP expression in cells plated on FN. These results indicate that the ECM regulates the induction of ALP expression by AsA in fibroblasts: FN enables them to express ALP in response to AsA through interaction with integrin alpha 5 beta 1, whereas type I collagen fibrils cause the suppression of ALP expression and overcome FN.
authors.affiliation: Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan. tabe@dent.kyushu-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Abe
authors.forename: Y
authors.initials: Y
authors.lastname: Abe
authors.forename: Y
authors.initials: Y
authors.lastname: Aida
authors.forename: Y
authors.initials: Y
authors.lastname: Hara
authors.forename: K
authors.initials: K
authors.lastname: Maeda
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000096:biosynthesis*; D000906:Antibodies / Q000276:immunology; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D005109:Extracellular Matrix / Q000502:physiology* / Q000648:ultrastructure; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology*; D005353:Fibronectins / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D017469:Receptors, Fibronectin / Q000037:antagonists & inhibitors / Q000276:immunology; D015854:Up-Regulation
chemical_list: D000906:Antibodies; D005353:Fibronectins; D017469:Receptors, Fibronectin; C011669:ascorbate-2-phosphate; C002195:3,4-dehydroproline; D003094:Collagen; D011392:Proline; D000469:Alkaline Phosphatase; D001205:Ascorbic Acid