A novel role of IL-15 in the development of osteoclasts: Inability to replace its activity with IL-2

Yoshiyasu Ogata, Akiko Kukita, Toshio Kukita, Mitunori Komine, Akira Miyahara, Sumio Miyazaki, Osamu Kohashi

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111 Citations (Scopus)


IL-15 shares many activities with IL-2 on stimulating lymphocytes, hematopoietic progenitor cells, and macrophages. However, the role of IL-15 in osteoclastogenesis has not been elucidated. The recent finding of abundant IL-15 in rheumatoid arthritis synovial fluids suggested a possible role for this cytokine in the pathological destruction of bone and prompted us to determine whether IL-15 stimulates osteoclast formation. IL-15 stimulated the formation of multinucleated osteoclast-like cells in rat bone marrow cultures. In stroma-free cultures, IL-15 increased the number of mononuclear preosteoclast-like cells in the early stage of osteoclast formation. The stimulation was observed even after treatment with IL-15 for only 24 or 48 h of culture. Moreover, low IL-15 concentration (0.1 ng/ml) strongly increased the level of calcitonin receptor mRNA of mononuclear preosteoclast-like cells. Although IL-15 is known as a potent stimulator of TNF-α, its activity was not abolished by addition of anti-TNF-α Ab. Interestingly, IL-2 and IL- 7, which utilize some IL-15R components, had no effect on osteoclast differentiation, but pretreatment with IL-2 or IL-7 of bone marrow cells before the addition of IL-15 inhibited the enhancing activity of IL-15. In summary, IL-15 has a novel activity to stimulate the differentiation of osteoclast progenitors into preosteoclasts, which cannot be replaced by IL-2 but may use components in common with IL-2R to mediate its effects.

Original languageEnglish
Pages (from-to)2754-2760
Number of pages7
JournalJournal of Immunology
Issue number5
Publication statusPublished - Mar 1 1999

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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