title: Beta-1 integrins mediate substrate dependent effects of 1alpha,25(OH)2D3 on osteoblasts.
abstract: Surface micron-scale and submicron scale features increase osteoblast differentiation and enhance responses of osteoblasts to 1,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)]. beta(1) integrin expression is increased in osteoblasts grown on Ti substrates with rough microarchitecture, and it is regulated by 1alpha,25(OH)(2)D(3) in a surface-dependent manner. To determine if beta(1) has a role in mediating osteoblast response, we silenced beta(1) expression in MG63 human osteoblast-like cells using small interfering RNA (siRNA). In addition, MG63 cells were treated with two different monoclonal antibodies to human beta(1) to block ligand binding. beta(1)-silenced MG63 cells grown on a tissue culture plastic had reduced alkaline phosphatase activity and levels of osteocalcin, transforming growth factor beta(1), prostaglandin E(2), and osteoprotegerin in comparison with control cells. Moreover, beta(1)-silencing inhibited the effects of surface roughness on these parameters and partially inhibited effects of 1alpha,25(OH)(2)D(3). Anti beta(1) antibodies decreased alkaline phosphatase but increase osteocalcin; effects of 1alpha,25(OH)(2)D(3) on cell number and alkaline phosphatase were reduced and effects on osteocalcin were increased. These findings indicate that beta(1) plays a major and complex role in osteoblastic differentiation modulated by either surface microarchitecture or 1alpha,25(OH)(2)D(3). The results also show that beta(1) mediates, in part, the synergistic effects of surface roughness and 1alpha,25(OH)(2)D(3).
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332-0363, USA.
authors.forename: Zvi
authors.initials: Z
authors.lastname: Schwartz
authors.forename: Bryan F
authors.initials: BF
authors.lastname: Bell
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Ge
authors.initials: G
authors.lastname: Zhao
authors.forename: Rene
authors.initials: R
authors.lastname: Olivares-Navarrete
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Boyan
mesh_terms: D002117:Calcitriol / Q000378:metabolism*; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D039641:Integrin beta Chains; D002117:Calcitriol