Ghrelin Fights Against Titanium Particle-Induced Inflammatory Osteolysis Through Activation of β-Catenin Signaling Pathway.

Aseptic loosening is a major complication of prosthetic joint surgery, in which exaggerated inflammation and impaired osteoblastogenesis are detected. Ghrelin is a recently discovered neuropeptide that is closely associated with inflammatory conditions and bone regeneration. Here, we report that titanium particles inhibited ghrelin expression in MC3T3-E1 cells. Furthermore, exogenous ghrelin effectively inhibited titanium particle-induced inflammation in vitro by interacting with its receptor GHSR1a; as an inhibitor of GHSR1a, Dlys repressed the function of ghrelin. Moreover, ghrelin attenuated the impairment of osteoblastogenesis and the exaggeration of osteolysis induced by titanium particles. Furthermore, the protective role of ghrelin in aseptic loosening might be associated with the Wnt/β-catenin signaling pathway. Collectively, these findings suggest that ghrelin might be a potential therapeutic target for wear-debris-induced inflammation and osteolysis.