title: PLAP-1/Asporin Positively Regulates FGF-2 Activity.
abstract: PLAP-1 is an extracellular matrix protein that is predominantly expressed in the periodontal ligament within periodontal tissue. It was previously revealed that PLAP-1 negatively regulates bone morphogenetic protein 2 and transforming growth factor β activity through direct interactions. However, the interaction between PLAP-1 and other growth factors has not been defined. Here, we revealed that PLAP-1 positively regulates the activity of fibroblast growth factor 2 (FGF-2), a critical growth factor in tissue homeostasis and repair. In this study, we isolated mouse embryonic fibroblasts (MEFs) from Plap-1(-/-) mice generated in our laboratory. Interestingly, Plap-1(-/-) MEFs exhibited enhanced responses to bone morphogenetic protein 2 but defective responses to FGF-2, and Plap-1 transfection into Plap-1(-/-) MEFs rescued these defective responses. In addition, binding assays revealed that PLAP-1 promotes FGF-2-FGF receptor 1 (FGFR1) complex formation by direct binding to FGF-2. Immunocytochemistry analyses revealed colocalization of PLAP-1 and FGF-2 in wild-type MEFs and reduced colocalization of FGF-2 and FGFR1 in Plap-1(-/-) MEFs compared with wild-type MEFs. Taken together, PLAP-1 positively regulates FGF-2 activity through a direct interaction. Extracellular matrix-growth factor interactions have considerable effects; thus, this approach may be useful in several regenerative medicine applications.
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Awata
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan satoru@dent.osaka-u.ac.jp.
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tsushima
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sakashita
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamaba
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kajikawa
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamashita
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takedachi
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yanagita
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kitamura
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Murakami
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000502:physiology
chemical_list: C511592:Aspn protein, mouse; D016326:Extracellular Matrix Proteins; C498812:Fgf20 protein, mouse; D005346:Fibroblast Growth Factors; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: BMP-2; cell differentiation; cell proliferation; extracellular matrix; growth factors; periodontal ligament