Direct Inhibition of Human RANK(+) Osteoclast Precursors Identifies a Homeostatic Function of IL-1 beta
DC Field | Value | Language |
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dc.contributor.author | Lee, Bitnara | - |
dc.contributor.author | Kim, Tae-Hwan | - |
dc.contributor.author | Jun, Jae-Bum | - |
dc.contributor.author | Yoo, Dae-Hyun | - |
dc.contributor.author | Woo, Jin-Hyun | - |
dc.contributor.author | Choi, Sung Jae | - |
dc.contributor.author | Lee, Young Ho | - |
dc.contributor.author | Song, Gwan Gyu | - |
dc.contributor.author | Sohn, Jeongwon | - |
dc.contributor.author | Park-Min, Kyung-Hyun | - |
dc.contributor.author | Ivashkiv, Lionel B. | - |
dc.contributor.author | Ji, Jong Dae | - |
dc.date.accessioned | 2022-12-20T11:18:37Z | - |
dc.date.available | 2022-12-20T11:18:37Z | - |
dc.date.created | 2022-08-26 | - |
dc.date.issued | 2010-11 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/173548 | - |
dc.description.abstract | IL-1 beta is a key mediator of bone resorption in inflammatory settings, such as rheumatoid arthritis (RA). IL-1 beta 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-IL-1R domain and common intracellular signaling molecules with TLRs that can directly inhibit early steps of human osteoclast differentiation, we tested whether IL-1 beta also has suppressive properties on osteoclastogenesis in primary human peripheral blood monocytes and RA synovial macrophages. Early addition of IL-1 beta, prior to or together with RANKL, strongly inhibited human osteoclastogenesis as assessed by generation of TRAP(+) multinucleated cells. IL-1 beta 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 beta rendered early-stage human OCPs refractory to RANK stimulation. Similar inhibitory effects of IL-1 beta were observed using RA synovial macrophages. One mechanism of RANK inhibition was IL-1 beta-induced proteolytic shedding of the M-CSF receptor c-Fms that is required for RANK expression. These results identify a homeostatic function of IL-1 beta in suppressing early OCPs that contrasts with its well-established role in promoting later stages of osteoclast differentiation. Thus, the rate of IL-1-driven 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. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | AMER ASSOC IMMUNOLOGISTS | - |
dc.title | Direct Inhibition of Human RANK(+) Osteoclast Precursors Identifies a Homeostatic Function of IL-1 beta | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Tae-Hwan | - |
dc.contributor.affiliatedAuthor | Jun, Jae-Bum | - |
dc.contributor.affiliatedAuthor | Yoo, Dae-Hyun | - |
dc.identifier.doi | 10.4049/jimmunol.1001591 | - |
dc.identifier.scopusid | 2-s2.0-78650661468 | - |
dc.identifier.wosid | 000283848000030 | - |
dc.identifier.bibliographicCitation | JOURNAL OF IMMUNOLOGY, v.185, no.10, pp.5926 - 5934 | - |
dc.relation.isPartOf | JOURNAL OF IMMUNOLOGY | - |
dc.citation.title | JOURNAL OF IMMUNOLOGY | - |
dc.citation.volume | 185 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 5926 | - |
dc.citation.endPage | 5934 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Immunology | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.subject.keywordPlus | INTERLEUKIN-1 RECEPTOR ANTAGONIST | - |
dc.subject.keywordPlus | TUMOR-NECROSIS-FACTOR | - |
dc.subject.keywordPlus | RHEUMATOID-ARTHRITIS | - |
dc.subject.keywordPlus | AUTOINFLAMMATORY DISEASE | - |
dc.subject.keywordPlus | DOWN-MODULATION | - |
dc.subject.keywordPlus | CSF-1 RECEPTOR | - |
dc.subject.keywordPlus | MAP KINASE | - |
dc.subject.keywordPlus | TNF-ALPHA | - |
dc.subject.keywordPlus | C-FMS | - |
dc.subject.keywordPlus | DIFFERENTIATION | - |
dc.identifier.url | https://www.jimmunol.org/content/185/10/5926 | - |
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