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Departments of
*
Microbiology,
Oral Maxillo-Facial Surgery, and
Pediatrics, Saga Medical School, Saga, Japan; and
§
Department of Second Anatomy, Faculty of Dentistry, Kyushu University, Fukuoka, Japan
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-
, its activity was not abolished by addition of
anti-TNF- 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.
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