title: Pharmacological GSK-3beta inhibition improves osteoblast differentiation on titanium surfaces.
abstract: Rough titanium surfaces enhance the activation of Wnt canonical signaling, a pathway required for osteoblast differentiation. The present study investigated the effects of GSK3b-inhibitor (2'Z,3'E)- 6-Bromoindirubin-3'-oxime (BIO) on osteoblastic differentiation on titanium surfaces with different topography and wettability. C2C12 cells were plated on pickled, acid-etched/sand-blasted (SLA), modified hydrophilic SLA titanium discs (modSLA) and stimulated with increasing doses of BIO. Activation of Wnt canonical signaling was measured with a reporter system. Gene expression was measured in the same cell system by Real Time PCR. Osteoblastic MC3T3 cells were then plated on discs with or without BIO and the expression of osteoblast specific genes was assessed by Real Time PCR. One mM BIO activated Wnt canonical signaling in C2C12 cells on all surfaces, and the highest effect was on rough surfaces. BIO markedly increased the expression of Osteoprotegerin and Osteocalcin in MC3T3 cells on rough surfaces at the concentration of 100 nM, and on all surfaces at the concentration of 1 mM. BIO enhances Wnt signaling activation and the expression of osteoblastic genes on rough surfaces and could be a viable approach to improve cell response to implant surfaces.
authors.affiliation: Department of Biomedical, Biotechnological, and Translational Sciences, University of Parma, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Lumetti
authors.affiliation: Department of Clinical and Experimental Medicine, University of Parma, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Ferrillo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Parma, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Mazzotta
authors.affiliation: Department of Biomedical, Biotechnological, and Translational Sciences, University of Parma, Italy.
authors.forename: G M
authors.initials: GM
authors.lastname: Macaluso
authors.affiliation: Department of Biomedical, Biotechnological, and Translational Sciences, University of Parma, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bonanini
authors.affiliation: Department of Clinical and Experimental Medicine, University of Parma, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Passeri
authors.affiliation: Department of Biomedical, Biotechnological, and Translational Sciences, University of Parma, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Galli
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000201:enzymology*; D015675:Osteocalcin / Q000096:biosynthesis; D053244:Osteoprotegerin / Q000096:biosynthesis; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry*; D060449:Wnt Signaling Pathway
chemical_list: D004791:Enzyme Inhibitors; D053244:Osteoprotegerin; C506031:Tnfrsf11b protein, mouse; D015675:Osteocalcin; D014025:Titanium; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3