Scheme 1

Schematic illustration showing the inhibition mechanism of osteogenesis in wear particle-induced osteolysis. Abnormal activation of glycogen synthesis kinase 3β (GSK-3β) triggered by Ti nanoparticles participates in the posttranslational modification and degradation of Gli1, which is the key transcription factor of osteogenesis in the Hedgehog pathway. In addition, inactivation of GSK-3β rescued Ti nanoparticle-induced osteogenesis inhibition as a result of increasing the accumulation of Gli1 and its translocation from the cytoplasm to the nucleus