title: Direct and indirect effects of microstructured titanium substrates on the induction of mesenchymal stem cell differentiation towards the osteoblast lineage.
abstract: Microstructured and high surface energy titanium substrates increase osseointegration in vivo. In vitro, osteoblast differentiation is increased, but effects of the surface directly on multipotent mesenchymal stem cells (MSCs) and consequences for MSCs in the peri-implant environment are not known. We evaluated responses of human MSCs to substrate surface properties and examined the underlying mechanisms involved. MSCs exhibited osteoblast characteristics (alkaline phosphatase, RUNX2, and osteocalcin) when grown on microstructured Ti; this effect was more robust with increased hydrophilicity. Factors produced by osteoblasts grown on microstructured Ti were sufficient to induce co-cultured MSC differentiation to osteoblasts. Silencing studies showed that this was due to signaling via alpha2beta1 integrins in osteoblasts on the substrate surface and paracrine action of secreted Dkk2. Thus, human MSCs are sensitive to substrate properties that induce osteoblastic differentiation; osteoblasts interact with these surface properties via alpha2beta1 and secrete Dkk2, which acts on distal MSCs.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332-0363, USA.
authors.forename: Rene
authors.initials: R
authors.lastname: Olivares-Navarrete
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Hyzy
authors.forename: Daphne L
authors.initials: DL
authors.lastname: Hutton
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Erdman
authors.forename: Marco
authors.initials: M
authors.lastname: Wieland
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Boyan
authors.forename: Zvi
authors.initials: Z
authors.lastname: Schwartz
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013499:Surface Properties / Q000187:drug effects; D014025:Titanium / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C498622:DKK2 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D014025:Titanium