IL-17 induces osteoclastogenesis from human monocytes alone in the absence of osteoblasts, which is potently inhibited by anti-TNF-alpha antibody: a novel mechanism of osteoclastogenesis by IL-17

J Cell Biochem. 2009 Nov 1;108(4):947-55. doi: 10.1002/jcb.22326.

Abstract

IL-17 is a proinflammatory cytokine crucial for osteoclastic bone resorption in the presence of osteoblasts or synoviocytes in rheumatoid arthritis. However, the role of IL-17 in osteoclastogenesis from human monocytes alone remains unclear. Here, we investigated the role of IL-17 in osteoclastogenesis from human monocytes alone and the direct effect of infliximab on the osteoclastogenesis induced by IL-17. Human peripheral blood mononuclear cells (PBMC) were cultured for 3 days with M-CSF. After non-adherent cells were removed, IL-17 was added with either infliximab or osteoprotegerin (OPG). Seven days later, adherent cells were stained for vitronectin receptor. On the other hand, CD11b-positive monocytes purified from PBMC were also cultured and stained as described above. CD11b-positive cells were cultured with TNF-alpha and receptor activator of NF-kappaB ligand (RANKL). In the cultures of both adherent cells and CD11b-positive cells, IL-17 dose-dependently induced osteoclastogenesis in the absence of soluble-RANKL. OPG or infliximab inhibited IL-17-induced osteoclastogenesis. Interestingly, in the culture of CD11b-positive cells, the osteoclastogenesis was more potently inhibited by infliximab than by OPG. TNF-alpha and RANKL synergistically induced osteoclastogenesis. The present study clearly demonstrated the novel mechanism by which IL-17 directly induces osteoclastogenesis from human monocytes alone. In addition, infliximab potently inhibits the osteoclastogenesis directly induced by IL-17.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • Bone Marrow Cells / cytology
  • CD11b Antigen / biosynthesis
  • Cell Adhesion
  • Humans
  • Infliximab
  • Integrin alphaVbeta3 / metabolism
  • Interleukin-17 / metabolism
  • Interleukin-17 / physiology*
  • Leukocytes, Mononuclear / cytology
  • Macrophages / metabolism
  • Male
  • Mice
  • Monocytes / cytology
  • Monocytes / metabolism*
  • Osteoblasts / metabolism*
  • Osteoclasts / metabolism*
  • RANK Ligand / metabolism
  • Tumor Necrosis Factor-alpha / chemistry*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • CD11b Antigen
  • Integrin alphaVbeta3
  • Interleukin-17
  • RANK Ligand
  • TNFSF11 protein, human
  • Tumor Necrosis Factor-alpha
  • Infliximab