Britanin inhibits titanium wear particle‑induced osteolysis and osteoclastogenesis

Wear particle‑induced osteolysis is a serious compli‑ cation that occurs in individuals with titanium (Ti)‑based implants following long‑term usage due to loosening of the implants. The control of excessive osteoclast differentiation and inflammation is essential for protecting against wear particle‑induced osteolysis. The present study evaluated the effect of britanin, a pseudoguaianolide sesquiterpene isolated from Inula japonica, on osteoclastogenesis in vitro and Ti particle‑induced osteolysis in vivo. The effect of britanin was examined in the osteoclastogenesis of mouse bone marrow‑derived macrophages (BMMs) using TRAP staining, RT‑PCR, western blotting and immunocytochemistry. The protective effect of britanin was examined in a mouse calvarial osteolysis model and evaluated using micro‑CT and histomorphometry. Britanin inhibited osteoclast differentia‑ tion and F‑actin ring formation in the presence of macrophage colony‑stimulating factor and receptor activator of nuclear factorkBligandinBMMs.Theexpressionofosteoclast‑specific marker genes, including tartrate‑resistant acid phosphatase, cathepsin K, dendritic cell‑specific transmembrane protein, matrix metallopeptidase 9 and nuclear factor of activated T‑cells cytoplasmic 1, in the BMMs was significantly reduced by britanin. In addition, britanin reduced the expression of B lymphocyte‑induced maturation protein‑1, which is a transcriptional repressor of negative osteoclastogenesis regulators, including interferon regulatory factor‑8 and B‑cell lymphoma 6. Conversely, britanin increased the expression levels of anti‑oxidative stress genes, namely nuclear factor erythroid‑2‑related factor 2, NAD(P)H quinone oxidoreduc‑ tase 1 and heme oxygenase 1 in the BMMs. Furthermore, the administration of britanin significantly reduced osteolysis in a Ti particle‑induced calvarial osteolysis mouse model. Based on these findings, it is suggested that britanin may be a poten‑ tial therapeutic agent for wear particle‑induced osteolysis and osteoclast‑associated disease.