Impaired Autophagy in the Fibroblasts by Titanium Particles Increased the Release of CX3CL1 and Promoted the Chemotactic Migration of Monocytes

Impaired Autophagy in the Fibroblasts by Titanium Particles Increased the Release of CX3CL1 and Promoted the Chemotactic Migration of Monocytes:

Abstract

Aseptic loosening (AL) is the most frequent cause of failure of total hip arthroplasties (THA). Prosthetic wear particle-induced monocyte recruitment to the periprosthetic tissue and subsequent inflammatory response are thought to be the major contribution to AL. Fibroblast is a dominant cell type in interfacial membrane (IFM) which is the main pathological feature of periprosthetic osteolysis in failed THAs. Considering the role of fibroblasts, as sentinel cells, in the synthesis of chemokines and regulation of inflammation, we hypothesize that fibroblasts might be involved in the monocyte recruitment in the pathogenesis of periprosthetic osteolysis associated with particle debris. This study explored the induction of fibroblasts on the monocyte recruitment. The results showed that titanium (Ti) particle-stimulated fibroblasts isolated from IFMs of loosened THAs significantly promoted the chemotactic migration of THP-1 cells by increasing the release of CX3CL1 (C-X3-C motif chemokine ligand 1). Further investigation demonstrated that Ti particle stimulation increased the expression of ADAM10 (ADAM metallopeptidase domain 10) by impairing autophagy in the fibroblasts and in turn increased the cleavage and shedding of CX3CL1. Thus, we propose a new insight to the pathogenesis of aseptic loosening which implies that autophagy-ADAM10-CX3CL1 signaling pathway in fibroblasts can be leveraged to alleviating inflammation caused by monocyte recruitment in aseptic loosening and improving performance of articulation of the joint device.