title: Matrix metalloproteinases MMP-2, -9 and tissue inhibitors TIMP-1, -2 expression and secretion by primary human osteoblast cells in response to titanium, zirconia, and alumina ceramics.
abstract: Osteogenic properties of bone cells are a key parameter governing osseointegration of implant devices. In this context, osteoblasts have a central role via extracellular matrix synthesis and remodeling that they regulate through different protease activity. In this study, we have analyzed the expression of two matrix metalloproteinases (MMPs): MMP-2 (72 kDa) and MMP-9 (92 kDa) and their specific tissue inhibitors TIMP-1 and TIMP-2 in primary human osteoblastic cells. The effect of titanium, zirconia, and alumina ceramics on the synthesis of these proteases was assessed using reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and zymographic analysis. Our results showed that osteoblasts express MMP-2 and -9 mRNA. Furthermore, MMP-2 mRNA expression was decreased by titanium and increased by alumina whereas zirconia did not have any significant effect. Conversely, MMP-9 mRNA expression was stimulated by titanium but decreased with zirconia, whereas alumina induced no significant changes. Zymographic analysis has evidenced pro-MMP-2 gelatinolytic activity in all cell populations with time-dependent increase profile; pro-MMP-9, however, was not detected. Enzyme-linked immunosorbent assay data confirmed the production of MMP-2 and very low levels of MMP-9. In addition, TIMP-1 was secreted in 24-h-cultured cells and increased to maximal level at 48-72 h whereas TIMP-2 levels were very low. The interactions between human osteoblasts and the studied biomaterials altered both MMP-2, -9 and TIMP-1expression indicating that biomaterials may influence osseointegration and bone remodeling.
authors.affiliation: Unité INSERM ERM 0203, IFR 53, UFR Odontologie-1, Faculté de Pharmacie/Médecine 1, Ave du Maréchal Juin, 51095 Reims Cedex, France. oumhamed@univ-reims.fr
authors.forename: Z
authors.initials: Z
authors.lastname: Oum'hamed
authors.forename: R
authors.initials: R
authors.lastname: Garnotel
authors.forename: Y
authors.initials: Y
authors.lastname: Josset
authors.forename: C
authors.initials: C
authors.lastname: Trenteseaux
authors.forename: D
authors.initials: D
authors.lastname: Laurent-Maquin
mesh_terms: D000537:Aluminum Oxide / Q000494:pharmacology*; D001483:Base Sequence; D002516:Ceramics / Q000494:pharmacology*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics* / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics* / Q000378:metabolism; D014025:Titanium / Q000494:pharmacology*; D015040:Zirconium / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D015040:Zirconium; D014025:Titanium; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000537:Aluminum Oxide; C028541:zirconium oxide