Interleukin-17A induces extracellular matrix protein expression in osteoblastic ROS17/2.8 cells

Akiko Kuwabara, Natsuko Tanabe, Takayuki Kawato, Hideki Tanaka, Kumiko Nakai, Toshimitsu Iinuma, Hidero Oki, Masafumi Motohashi, Masao Maeno

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4 Citations (Scopus)


Interleukin (IL)-17 plays an important role in many autoimmune and inflammatory diseases. We recently demonstrated the various direct and indirect effects of IL-17A on osteoclastogenesis. However, the effect of IL-17A on bone matrix formation by osteoblasts is unclear. Therefore, we examined the effect of IL-17A on IL-17 receptor (IL-17R), extracellular matrix protein (ECMP), and cyclooxygenase (COX) expression; prostaglandin (PG) E 2 production; alkaline phosphatase (ALPase) activity; and mineralized nodule formation in osteoblastic ROS17/2.8 cells. We also examined the indirect effect of PGE 2 on IL-17-induced ECMP expression using NS398, a specific inhibitor of COX-2 activity. Cells were cultured with 0 (control), 1, 10, or 100 ng/mL IL-17A in the presence or absence of 50 ng/mL neutralizing anti-IL-17A antibodies or 1 μM NS398. IL-17RA, IL-17RC, type I collagen, bone sialoprotein (BSP), osteocalcin, osteopontin, COX-1, and COX-2 expression was examined by real-time PCR and Western blotting. PGE 2 production was examined by ELISA. The expression of IL-17RA, type I collagen, BSP, osteocalcin, osteopontin, and COX-2, and PGE 2 production were increased significantly in the presence of IL-17A, whereas the expression of IL-17RC and COX-1, cell proliferation, ALPase activity, and mineralized nodule formation were unaffected. Anti-IL-17 antibodies blocked IL-17Ainduced ECMP expression. NS398 blocked IL-17A-induced PGE 2 production, but it did not affect IL-17Ainduced ECMP expression. These results suggest that IL-17A stimulates ECMP expression via IL-17RC and/or IL-17A-induced IL-17RA in osteoblasts; however, mineralized nodule formation by the cells was unaffected by the addition of IL-17A. Furthermore, our results indicate that the stimulatory effect of IL-17A on ECMP expression is independent of the indirect effect of IL-17A-induced PGE 2.

Original languageEnglish
Pages (from-to)247-258
Number of pages12
JournalJournal of Hard Tissue Biology
Issue number3
Publication statusPublished - 2011


  • Bone sialoprotein
  • Interleukin-17A
  • Osteoblasts
  • Osteocalcin
  • Osteopontin
  • Type I collagen


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