Metallic implants have great application in clinical orthopedics. Implants wear out in vivo due to long-term mechanical loading. The formation of wear debris is one of the long-term complications of prosthesis. In the case of artificial joint replacement in particular, aseptic loosening is the most common reason for secondary revision surgery. Previous studies suggested that wear debris caused aseptic loosening mainly by promoting osteolysis around the prosthesis. In this study, titanium particles, the most commonly used particles in clinical practice, were selected to simulate wear debris and explore the influence of titanium particles on osteogenic differentiation of mesenchymal stem cells. Our results show that titanium particles can significantly inhibit osteogenic differentiation in a dose-dependent manner. While engaged in preliminary exploration of the underlying mechanisms, we found that titanium particles significantly affect phosphorylation of ERK1/2, a key component of MAPK signaling. This suggests that the MAPK signaling pathway is involved in the inhibition of osteogenic differentiation by titanium particles.