Lipoteichoic acid from Staphylococcus aureus attenuates differentiation of pre-osteoclast into mature osteoclast

Bacterial virulence factors regulate differentiation and functions of osteoclasts, which mediate the bone-resorptive process. Here, we investigated the effect of a major cell wall virulence factor of Gram-positive bacteria, lipoteichoic acid (LTA), on the osteoclast differentiation. Highly-pure and structurally-intact LTA was prepared from Staphylococcus aureus through sequential application of organic solvent extraction and hydrophobic-interaction column chromatography followed by ion-exchange column chromatography. Osteoclast precursors were prepared from C57BL/6 mouse bone marrow cells using M-CSF and RANKL. Staphylococcal LTA suppressed the differentiation of osteoclast precursors to mature osteoclasts concordantly with an inhibition of the bone-resorptive capacity. Meanwhile, LTA augmented the phagocytic and inflammatory potential of the pre-osteoclasts. The LTA inhibition of osteoclast differentiation appears to be mediated through Toll-like receptor 2 (TLR2), and interestingly both MyD88-dependent and -independent signaling pathways. Furthermore, LTA reduced phosphorylation of ERK and JNK during the osteoclast differentiation process followed by a decreased DNA-binding activity of AP-1. Conclusively, our results suggest that LTA from S. aureus attenuates the differentiation of pre-osteoclast to mature osteoclast through TLR2 with partial involvement of MyD88 signaling pathways.