Inhibitory effect of icariin on Ti-induced inflammatory osteoclastogenesis.

Background: Wear particle-induced periprosthetic osteolysis that results in aseptic loosening is the most common cause of long-term failure after total joint replacement.

Materials and Methods: Icariin (ICA), a flavonoid isolated from Epimedium pubescens, inhibits osteoclast formation, but its effects on wear particle-induced inflammatory osteoclastogenesis remains unclear. We investigated the role of ICA in the regulation of osteoclast differentiation in a murine macrophage cell line (RAW264.7), which is stimulated by titanium (Ti) particles and the receptor activator of NF-κB ligand.

Results: ICA effectively inhibited osteoclast formation and bone resorption in the differentiation medium. ICA (10(-7) mol/L) significantly reduced the number of tartrate-resistant acid phosphatase-positive cells compared with the control, and significantly reduced the percentage of the surface covered by resorption lacunae. Quantitative real-time polymerase chain reaction analysis showed that ICA inhibited messenger RNA expression for the receptor activator of nuclear factor-κB, cathepsin K, tartrate-resistant acid phosphatase-positive, and matrix metalloproteinase-9 in RAW264.7 cells stimulated by Ti particles and receptor activator of NF-κB ligand. ICA also reduced pro-inflammatory cytokine expression of interleukin-1β and tumor necrosis factor-α in RAW264.7 cells cultured with Ti particles. In addition, incubation with cholecystokinin-8 showed that ICA had no toxic effects on RAW264.7 cells.

Conclusions: ICA possibly elicited inhibitory effects on inflammatory osteoclastogenesis induced by Ti particles, indicating that ICA may be useful for the prevention and treatment of wear particle-induced osteolysis.

(Copyright © 2014 Elsevier Inc. All rights reserved.)