Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0309206 on July 14, 2009

Published online before print July 14, 2009
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(Journal of Leukocyte Biology. 2009;86:823-831.)
© 2009 Society for Leukocyte Biology

Impaired osteoclastogenesis by staphylococcal lipoteichoic acid through Toll-like receptor 2 with partial involvement of MyD88

Jihyun Yang*, Young Hee Ryu*, Cheol-Heui Yun{dagger} and Seung Hyun Han*,{ddagger},1

* Department of Oral Microbiology and Immunology, Dental Research Institute, and BK21 Program, School of Dentistry, and
{dagger} Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, and
{ddagger} International Vaccine Institute, Seoul National University Research Park, Seoul, Republic of Korea

1. Correspondence: Seoul National University School of Dentistry, Oral Microbiology and Immunology, 28 Yongon-Dong, Chongno-Gu, Seoul 110-749, Republic of Korea. E-mail: shhan-mi{at}snu.ac.kr

ABSTRACT

Degenerative bone disease, marked by excessive loss of calcified matrix, is often associated with bacterial infections. Osteoclasts, which mediate the bone-resorptive process, are derived mainly from myeloid precursor cells of the monocyte/macrophage lineage, from which cells with phagocytic and inflammatory capacities may alternatively arise. Here, we investigated the effect of LTA, a major cell-wall virulence factor of Gram-positive bacteria, on osteoclast differentiation. Osteoclast precursors were prepared from C57BL/6 mouse BM using M-CSF and RANKL. When osteoclastogenesis was induced in the presence of staphylococcal LTA, LTA dose-dependently inhibited the differentiation of osteoclast precursors to mature osteoclasts. A corresponding inhibition of bone-resorptive function was observed in the reduced resorption area on calcium phosphate-coated culture plates. In contrast, the phagocytic and inflammatory potential of the osteoclast precursors increased in the presence of LTA. TLR2, known to recognize LTA, might be essential for the LTA inhibition of osteoclastogenesis, as the inhibition did not occur in the precursors from TLR2-deficient mice. Importantly, MyD88-dependent and MyD88-independent pathways would participate in the inhibition, as determined using MyD88-deficient cells. Moreover, LTA inhibited phosphorylation of ERK and JNK in osteoclast precursors stimulated with M-CSF and RANKL, concomitantly with a decreased DNA-binding activity of AP-1. These results suggest that staphylococcal LTA inhibits osteoclast differentiation primarily through TLR2 but also in part through MyD88 signaling, which in turn, inhibits activation of ERK, JNK, and AP-1.

Key Words: osteoclast differentiation • Staphylococcus aureus • pathogen-associated molecular pattern • pattern-recognition receptor