title: Bone morphogenetic protein-2 is a regulator of cell adhesion.
abstract: Bone morphogenetic proteins (BMPs) are a group of peptide growth factors closely related to transforming growth factors-beta. The BMPs are suggested to play an essential role in bone development and they are strong candidate molecules to be used clinically to improve fracture healing. BMPs are also involved in the differentiation of several other tissues during embryogenesis. Here, we show that human recombinant BMP-2 regulates cell-matrix interactions by modifying the expression of integrin-type receptors. The synthesis of alpha3 integrin was down-regulated by BMP-2 in two osteogenic sarcoma-derived cell lines, Saos-2 and HOS, and also in human fetal chondrocytes. BMP-2 had no effect on the expression of alpha1, alpha2, alpha5, alpha6, and alphaV integrins. BMP-2 reduced the expression of alpha3 integrin subunit at mRNA level. Laminin-5 was shown to be the ligand for alpha3beta1 integrin on Saos cells and BMP-2 decreased the ability of Saos cells to attach to it. These results suggest that BMP-2 has a specific effect on the alpha3beta1 integrin-mediated cell adhesion to laminin-5. Given the fact that BMP-2 is expressed in osteosarcomas, in addition to in bone, this mechanism is putatively important especially in bone development and tumors. We also studied the effect of BMP-2 on a human keratinocyte cell line, HaCaT. In HaCaT cells, the expression of alpha2 integrin was strongly down-regulated by BMP-2, whereas its effect on the expression of alpha3 integrin was smaller. We suggest that the effects of BMP-2 may be partially mediated by specifically altered cell adhesion.
authors.affiliation: Department of Medical Biochemistry and MediCity Research Laboratory, University of Turku, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Nissinen
authors.forename: L
authors.initials: L
authors.lastname: Pirilä
authors.forename: J
authors.initials: J
authors.lastname: Heino
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D039421:Integrin alpha2; D039422:Integrin alpha3; D039201:Integrin alpha3beta1; D016023:Integrins / Q000378:metabolism*; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000097794:Kalinin
chemical_list: D015703:Antigens, CD; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D015815:Cell Adhesion Molecules; D039421:Integrin alpha2; D039422:Integrin alpha3; D039201:Integrin alpha3beta1; D016023:Integrins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000097794:Kalinin; C525718:BMP2 protein, human; C499469:recombinant human bone morphogenetic protein-2