Polycan suppresses osteoclast differentiation and titanium particle-induced osteolysis in mice

Particle-induced osteolysis is a major issue, and it is most likely the result of enhanced osteoclast activation in the pathogenesis of various skeletal diseases. This study investigated whether the inhibitory effect that Polycan has on osteoclast differentiation can be used to treat osteolysis induced by titanium (Ti) particles. To this end, the effects of Polycan were examined in terms of the cytotoxicity, osteoclast differentiation, cytokine expression, and Ti-induced calvarial osteolysis. Polycan had no significant cytotoxic effects on bone marrow macrophages (BMMs) but instead increased BMM proliferation. High levels of interleukin (IL)-6, IL-12, and macrophage colony-stimulating factor (M-CSF) were expressed in BMM cells in the presence of Polycan, suggesting that Polycan drives the differentiation of BMMs into M1 macrophages. Polycan significantly inhibited osteoclast differentiation induced by M-CSF and the receptor activator of nuclear factor kappa-B ligand (RANKL). The expression levels of the osteoclast marker genes significantly decreased, and Polycan induced and maintained the expression of IL-12, which suppressed osteoclast differentiation. In contrast, the RANKL signaling pathway was not inhibited by Polycan. An in vivo calvarial osteolysis model revealed that Polycan significantly decreased the osteoclast numbers and suppressed osteolysis. Our results suggest that the natural compound Polycan is a good candidate for therapeutic intervention against enhanced osteoclast differentiation and Ti particle-induced osteolysis.