Lipopolysaccharide supports survival and fusion of preosteoclasts independent of TNF-α, IL-1, and RANKL

Authors

  • Koji Suda,

    1. Department of Bioengineering, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama, Japan
    Search for more papers by this author
    • *

      Koji Suda is a Research Fellow of the Japan Society for the Promotion of Science.

  • Je-Tae Woo,

    1. Department of Bioengineering, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama, Japan
    Search for more papers by this author
  • Masamichi Takami,

    1. Department of Bioengineering, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama, Japan
    Search for more papers by this author
  • Patrick M. Sexton,

    1. Howard Florey Institute of Experimental Physiology and Medicine, The University of Melbourne, Victoria, Australia
    Search for more papers by this author
    • **

      Patrick M. Sexton is a Senior Research Fellow of the National Health and Medical Research Council of Australia.

  • Kazuo Nagai

    Corresponding author
    1. Department of Bioengineering, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama, Japan
    • Department of Bioengineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
    Search for more papers by this author

Abstract

Lipopolysaccharide (LPS), a cell component of Gram-negative bacteria, is a pathogen of inflammatory bone loss. To examine the effects of LPS on the survival and fusion of osteoclasts, mononuclear osteoclasts (preosteoclasts, pOCs) were collected from a mouse co-culture system and cultured in the presence or absence of LPS. Most pOCs died within 24 h in the absence of any stimulus. LPS as well as receptor activator of NF-κB ligand (RANKL) supported the survival of pOCs, and induced their fusion to form multinucleated cells (MNCs). Like authentic osteoclasts, MNCs induced by LPS expressed calcitonin receptors, and formed actin rings on culture plates. LPS-induced MNC formation in pOC cultures was observed even in the presence of osteoprotegerin and interleukin (IL)-1-receptor antagonists. MNC formation was also stimulated by LPS in pOC cultures prepared from tumor necrosis factor (TNF)-receptor-I or TNF-receptor-II deficient mice. LPS induced the degradation of IκB in pOCs within 20 min. Lactacystin, an inhibitor of NF-κB activation, and wortmannin, an inhibitor of phosphatidylinositol-3 kinase, strongly inhibited LPS-induced MNC formation in pOC cultures. LPS induced pit-forming activity of pOCs in the presence of macrophage-colony stimulating factor (M-CSF). These findings suggest that LPS stimulates the survival and fusion of pOCs, independent of RANKL, IL-1 or TNF-α action. Activation of NF-κB and phosphatidylinositol-3 kinase appeared to be involved in LPS-induced effects on pOCs. These observations suggest that LPS is involved directly in inflammatory bone loss, and also indirectly through the production of LPS-induced host factors such as IL-1 and TNF-α. J. Cell. Physiol. 190: 101–108, 2002. © 2002 Wiley-Liss, Inc.

Ancillary