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.
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.
Yago
Toru
T
Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo 162-0054, Japan. toruyago@ior.twmu.ac.jp
Nanke
Yuki
Y
Ichikawa
Naomi
N
Kobashigawa
Tsuyoshi
T
Mogi
Makio
M
Kamatani
Naoyuki
N
Kotake
Shigeru
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology; D039481:CD11b Antigen / Q000096:biosynthesis; D002448:Cell Adhesion; D006801:Humans; D000069285:Infliximab; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D039481:CD11b Antigen; D039302:Integrin alphaVbeta3; D020381:Interleukin-17; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab