Periprosthetic osteolysis caused by wear particles is the main factor that affects the long-term efficacy of artificial joint replacement, and macrophages play a vital role in the pathogenesis of periprosthetic osteolysis, while the potential mechanism underlying this is still unclear. To investigate the underlying role of miR-377 in wear particle-induced osteolysis (PIO), blood samples from patients undergoing arthroplasty were collected for analyzing the correlation between miR-377 expression and the clinicopathological parameters of PIO. Peripheral blood macrophages were obtained to compare the miR-377 and receptor activator of NF-κB ligand (RANKL) expressions. Bone marrow macrophages (BMMs) following titanium (Ti) particle treatment and/or miR-377 mimic transfection were used. The expressions of RANKL, pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) and the osteoclast-related molecules tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CTSK) were determined using real-time polymerase chain reaction or western blotting or enzyme-linked immunosorbent assay or TRAP staining, when appropriate. The interaction between miR-377 and RANKL was assessed by luciferase reporter assay. The in vivo role of miR-377 in PIO was evaluated using a mouse calvarial osteolysis model. There were significant differences in downregulated miR-377 expression between the different numbers of particles in the joint prostheses. The Ti particle treatment increased pro-inflammatory cytokine levels, downregulated RANKL and increased osteoclast activity in BMMs, while miR-377 overexpression led to the opposite effect. Taken together, miR-377 downregulated the target gene RANKL, resulting in PIO inhibition. MiR-377 relieved PIO by negatively regulating RANKL.
Keywords: miR-377; osteolysis; pro-inflammatory cytokines, RANKL, wear particle.
© 2019 International Federation for Cell Biology.