Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6 - PubMed (original) (raw)

Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6

T Tamura et al. Proc Natl Acad Sci U S A. 1993.

Abstract

It has been reported that soluble interleukin (IL)-6 receptor (sIL-6R) is detected in the serum of healthy individuals and its level is increased in patients with multiple myeloma and human immunodeficiency virus infection. Although several reports have suggested that sIL-6R potentiates IL-6 action, its physiological role remains unclear. In this study, we examined the role of sIL-6R on osteoclast formation by IL-6, using a coculture of mouse osteoblasts and bone marrow cells. Neither recombinant mouse IL-6 (mIL-6) nor mouse sIL-6R (smIL-6R) induced osteoclast-like multinucleated cell (MNC) formation when they were added separately. In contrast, simultaneous treatment with mIL-6 and smIL-6R strikingly induced MNC formation. These MNCs satisfied major criteria of authentic osteoclasts, such as tartrate-resistant acid phosphatase (TRAP) activity, calcitonin receptors, and pit formation on dentine slices. The MNC formation induced by mIL-6 and smIL-6R was dose-dependently inhibited by adding monoclonal anti-mouse IL-6R antibody (MR16-1). It is likely that osteoblasts and osteoclast progenitors are capable of transducing a signal from a complex of IL-6 and sIL-6R through gp130, even though they may have no or a very small number of IL-6Rs. Factors such as IL-11, oncostatin M, and leukemia inhibitory factor, which are known to exert their functions through gp130 (the signal-transducing chain of IL-6R), also induced MNC formation in our coculture system. These results suggest that increased circulating or locally produced sIL-6R induces osteoclast formation in the presence of IL-6 mediated by a mechanism involving gp130. This may play an important physiological or pathological role in conditions associated with increased osteoclastic bone resorption.

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References

    1. Endocrinology. 1988 Apr;122(4):1373-82 - PubMed
    1. J Bone Miner Res. 1993 Aug;8(8):953-60 - PubMed
    1. Endocrinology. 1988 Nov;123(5):2600-2 - PubMed
    1. Eur J Immunol. 1988 Nov;18(11):1797-801 - PubMed
    1. Blood. 1989 Feb;73(2):517-26 - PubMed

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