Triacylated lipopeptide, a component of Gram-positive bacteria, induces osteoclastogenesis in the absence of RANKL and resorbs calvarial bone in vivo through Toll-like receptor 2

To study the involvement of lipopeptide, a component of Gram-positive bacteria, in the pathogenesis of inflammatory osteolysis including periodontitis and osteomyelitis, we investigated whether lipopeptide influenced the differentiation and activation of osteoclasts. Pam3CSK4, a synthetic triacylated lipopeptide which has been proved to activate macrophages through TLR2, stimulated osteoclastogenesis at all the concentrations examined (between 10 and 1000 ng/ml), without adding RANKL exogenously, in bone marrow-derived preosteoclasts. Moreover, local injection of Pam3CSK4 to wild-type mouse induced osteolysis in calvaria, which was not observed in TLR2-null mouse, indicating that bone resorption in vivo also occurred through a TLR2-dependent mechanism. These findings demonstrate an important role of triacylated lipopeptide in differentiation and activation of osteoclasts which results in pathological bone destruction through TLR2 ligation.