Study of GSK3b inhibitors SB415286 and SB216763 to improve osteoblastic differentiation on microstructured titanium.

ABSTRACT

Rough titanium surfaces enhance cell response to activation of Wnt canonical signalling, a pathway required for osteoblast differentiation. The present study investigated the effects of GSK3ß-inhibitors SB216763 and SB415286 on osteoblastic differentiation on titanium surfaces with different topography and wettability. Osteoblastic MC3T3 cells were plated on smooth (Pickled), sand-blasted/acid-etched (SLA) or hyper hydrophilic SLA (modSLA) titanium discs and transfected with a reporter vector sys-tem for Wnt canonical signalling. Cells were also seeded in the presence or in the absence of GSK3b-inhibitors SB216763 or SB415286 and their viability, morphology and the expression of Wnt target and osteoblast specific genes was assessed by Real Time PCR. Inhibitors altered cell morphology and mostly reduced cell viability at high concentration. SB415286 markedly increased the expression of ALP in MC3T3 cells on rough surfaces at the concentration of 100 nM before decreasing its expression at higher concentrations. OCN expression was unaffected. Increasing concentrations of SB216763 increased the expression of ALP in MC3T3 cells on rough surfaces but OCN expression was not changed at any con-centration. SB216763 and SB415286 inhibitors should be further investigated as potential tools to improve cell differentiation on titanium surfaces for endosseous implants.