{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T14:58:47Z","timestamp":1777561127045,"version":"3.51.4"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2010,11,1]],"date-time":"2010-11-01T00:00:00Z","timestamp":1288569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IL-1\u03b2 is a key mediator of bone resorption in inflammatory settings, such as rheumatoid arthritis (RA). IL-1\u03b2 promotes osteoclastogenesis by inducing RANKL expression on stromal cells and synergizing with RANKL to promote later stages of osteoclast differentiation. Because IL-1Rs share a cytosolic Toll\u2013IL-1R domain and common intracellular signaling molecules with TLRs that can directly inhibit early steps of human osteoclast differentiation, we tested whether IL-1\u03b2 also has suppressive properties on osteoclastogenesis in primary human peripheral blood monocytes and RA synovial macrophages. Early addition of IL-1\u03b2, prior to or together with RANKL, strongly inhibited human osteoclastogenesis as assessed by generation of TRAP+ multinucleated cells. IL-1\u03b2 acted directly on human osteoclast precursors (OCPs) to strongly suppress expression of RANK, of the costimulatory triggering receptor expressed on myeloid cells 2 receptor, and of the B cell linker adaptor important for transmitting RANK-induced signals. Thus, IL-1\u03b2 rendered early-stage human OCPs refractory to RANK stimulation. Similar inhibitory effects of IL-1\u03b2 were observed using RA synovial macrophages. One mechanism of RANK inhibition was IL-1\u03b2\u2013induced proteolytic shedding of the M-CSF receptor c-Fms that is required for RANK expression. These results identify a homeostatic function of IL-1\u03b2 in suppressing early OCPs that contrasts with its well-established role in promoting later stages of osteoclast differentiation. Thus, the rate of IL-1\u2013driven bone destruction in inflammatory diseases, such as RA, can be restrained by its direct inhibitory effects on early OCPs to limit the extent of inflammatory osteolysis.<\/jats:p>","DOI":"10.4049\/jimmunol.1001591","type":"journal-article","created":{"date-parts":[[2010,10,9]],"date-time":"2010-10-09T03:04:32Z","timestamp":1286593472000},"page":"5926-5934","source":"Crossref","is-referenced-by-count":45,"title":["Direct Inhibition of Human RANK+ Osteoclast Precursors Identifies a Homeostatic Function of IL-1\u03b2"],"prefix":"10.1093","volume":"185","author":[{"given":"Bitnara","family":"Lee","sequence":"first","affiliation":[{"name":"Hospital for Rheumatic Diseases, Hanyang University , Seoul ,","place":["South Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae-Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Hospital for Rheumatic Diseases, Hanyang University , Seoul ,","place":["South Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Bum","family":"Jun","sequence":"additional","affiliation":[{"name":"Hospital for Rheumatic Diseases, Hanyang University , Seoul ,","place":["South Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dae-Hyun","family":"Yoo","sequence":"additional","affiliation":[{"name":"Hospital for Rheumatic Diseases, Hanyang University , Seoul ,","place":["South Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Hyun","family":"Woo","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, College of Medicine, Korea University , Seoul ,","place":["South Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Jae","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, College of Medicine, Korea University , Seoul ,","place":["South Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, College of Medicine, Korea University , Seoul ,","place":["South Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwan Gyu","family":"Song","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, College of Medicine, Korea University , Seoul ,","place":["South Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeongwon","family":"Sohn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, Korea University , Seoul ,","place":["South Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung-Hyun","family":"Park-Min","sequence":"additional","affiliation":[{"name":"Arthritis and Tissue Degeneration Program, Hospital for Special Surgery , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lionel B","family":"Ivashkiv","sequence":"additional","affiliation":[{"name":"Arthritis and Tissue Degeneration Program, Hospital for Special Surgery , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong Dae","family":"Ji","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, College of Medicine, Korea University , Seoul ,","place":["South Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2010,11,15]]},"reference":[{"key":"2025032412093736000_r1","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/nri2062","article-title":"Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems","volume":"7","author":"Takayanagi","year":"2007","journal-title":"Nat. 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