{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:42:57Z","timestamp":1793054577906,"version":"4.5.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1993,12,15]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1073\/pnas.90.24.11924","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:36:45Z","timestamp":1149064605000},"page":"11924-11928","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":674,"title":["Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6."],"prefix":"10.1073","volume":"90","author":[{"given":"T","family":"Tamura","sequence":"first","affiliation":[{"name":"Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Udagawa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Miyaura","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Koishihara","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Ohsugi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Kumaki","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Taga","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1993,12,15]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.90.24.11924","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:28:23Z","timestamp":1649856503000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.90.24.11924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,12,15]]},"references-count":0,"journal-issue":{"issue":"24","published-print":{"date-parts":[[1993,12,15]]}},"alternative-id":["10.1073\/pnas.90.24.11924"],"URL":"https:\/\/doi.org\/10.1073\/pnas.90.24.11924","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,12,15]]},"assertion":[{"value":"1993-12-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}