{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:10:57Z","timestamp":1783548657190,"version":"3.55.0"},"reference-count":52,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bone"],"published-print":{"date-parts":[[2009,10]]},"DOI":"10.1016\/j.bone.2009.06.004","type":"journal-article","created":{"date-parts":[[2009,6,13]],"date-time":"2009-06-13T09:21:52Z","timestamp":1244884912000},"page":"661-668","source":"Crossref","is-referenced-by-count":28,"title":["Reduction of particle-induced osteolysis by interleukin-6 involves anti-inflammatory effect and inhibition of early osteoclast precursor differentiation"],"prefix":"10.1016","volume":"45","author":[{"given":"Michael","family":"Darowish","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra'Kerry","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan V.","family":"Bukata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Gelinas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willis","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Flick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward M.","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regis J.","family":"O'Keefe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bone.2009.06.004_bib1","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.2106\/00004623-199411000-00010","article-title":"Isolation and characterization of debris in membranes around total joint prostheses","volume":"76","author":"Margevicius","year":"1994","journal-title":"J. Bone Joint Surg. Am."},{"key":"10.1016\/j.bone.2009.06.004_bib2","first-page":"114","article-title":"A biochemical, histologic, and immunohistologic analysis of membranes obtained from failed cemented and cementless total knee arthroplasty","author":"Chiba","year":"1994","journal-title":"Clin. Orthop. Relat. Res."},{"key":"10.1016\/j.bone.2009.06.004_bib3","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1302\/0301-620X.83B6.10905","article-title":"The osteoclastogenic molecules RANKL and RANK are associated with periprosthetic osteolysis","volume":"83","author":"Haynes","year":"2001","journal-title":"J. Bone Joint Surg. Br."},{"key":"10.1016\/j.bone.2009.06.004_bib4","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1136\/ard.2003.008458","article-title":"Joint erosion in rheumatoid arthritis: interactions between tumour necrosis factor alpha, interleukin 1, and receptor activator of nuclear factor kappaB ligand (RANKL) regulate osteoclasts","volume":"63","author":"O'Gradaigh","year":"2004","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.bone.2009.06.004_bib5","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1084\/jem.190.12.1741","article-title":"Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors","volume":"190","author":"Arai","year":"1999","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.bone.2009.06.004_bib6","doi-asserted-by":"crossref","first-page":"11846","DOI":"10.1074\/jbc.M512624200","article-title":"Tumor necrosis factor-alpha increases circulating osteoclast precursor numbers by promoting their proliferation and differentiation in the bone marrow through up-regulation of c-Fms expression","volume":"281","author":"Yao","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bone.2009.06.004_bib7","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1359\/JBMR.0301233","article-title":"RANK signaling is not required for TNFalpha-mediated increase in CD11(hi) osteoclast precursors but is essential for mature osteoclast formation in TNFalpha-mediated inflammatory arthritis","volume":"19","author":"Li","year":"2004","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2009.06.004_bib8","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/art.11419","article-title":"Systemic tumor necrosis factor alpha mediates an increase in peripheral CD11b(high) osteoclast precursors in tumor necrosis factor alpha-transgenic mice","volume":"50","author":"Li","year":"2004","journal-title":"Arthritis Rheum."},{"key":"10.1016\/j.bone.2009.06.004_bib9","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/16852","article-title":"OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis","volume":"397","author":"Kong","year":"1999","journal-title":"Nature"},{"key":"10.1016\/j.bone.2009.06.004_bib10","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1172\/JCI11066","article-title":"Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha","volume":"106","author":"Cenci","year":"2000","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.bone.2009.06.004_bib11","doi-asserted-by":"crossref","first-page":"20659","DOI":"10.1074\/jbc.M010153200","article-title":"Receptor activator of NF-kappa B and osteoprotegerin expression by human microvascular endothelial cells, regulation by inflammatory cytokines, and role in human osteoclastogenesis","volume":"276","author":"Collin-Osdoby","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bone.2009.06.004_bib12","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1172\/JCI11176","article-title":"TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand","volume":"106","author":"Lam","year":"2000","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.bone.2009.06.004_bib13","doi-asserted-by":"crossref","first-page":"4858","DOI":"10.1074\/jbc.275.7.4858","article-title":"Tumor necrosis factor-alpha induces differentiation of and bone resorption by osteoclasts","volume":"275","author":"Azuma","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bone.2009.06.004_bib14","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1084\/jem.191.2.275","article-title":"Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF\/RANKL\u2013RANK interaction","volume":"191","author":"Kobayashi","year":"2000","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.bone.2009.06.004_bib15","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0736-0266(02)00106-7","article-title":"Two distinct cellular mechanisms of osteoclast formation and bone resorption in periprosthetic osteolysis","volume":"21","author":"Sabokbar","year":"2003","journal-title":"J. Orthop. Res."},{"key":"10.1016\/j.bone.2009.06.004_bib16","first-page":"485","article-title":"Interleukin-6 in aseptic loosening of total hip replacement prostheses","volume":"20","author":"Konttinen","year":"2002","journal-title":"Clin. Exp. Rheumatol."},{"key":"10.1016\/j.bone.2009.06.004_bib17","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/S0736-0266(03)00153-0","article-title":"PGE2 and IL-6 production by fibroblasts in response to titanium wear debris particles is mediated through a Cox-2 dependent pathway","volume":"22","author":"Bukata","year":"2004","journal-title":"J. Orthop. Res."},{"key":"10.1016\/j.bone.2009.06.004_bib18","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1002\/(SICI)1097-4636(199823)43:3<234::AID-JBM3>3.0.CO;2-O","article-title":"Joint fluid from patients with failed total hip arthroplasty stimulates pit formation by mouse osteoclasts on dentin slices","volume":"43","author":"Kim","year":"1998","journal-title":"J. Biomed. Mater. Res."},{"key":"10.1016\/j.bone.2009.06.004_bib19","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/jbmr.5650110113","article-title":"Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation","volume":"11","author":"Kotake","year":"1996","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2009.06.004_bib20","doi-asserted-by":"crossref","first-page":"3517","DOI":"10.4049\/jimmunol.143.11.3517","article-title":"IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice","volume":"143","author":"Aderka","year":"1989","journal-title":"J. Immunol."},{"key":"10.1016\/j.bone.2009.06.004_bib21","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1128\/IAI.69.2.744-750.2001","article-title":"Interleukin-6 deficiency increases inflammatory bone destruction","volume":"69","author":"Balto","year":"2001","journal-title":"Infect. Immun."},{"key":"10.1016\/j.bone.2009.06.004_bib22","doi-asserted-by":"crossref","first-page":"11535","DOI":"10.1074\/jbc.M607999200","article-title":"Interleukin-6 directly inhibits osteoclast differentiation by suppressing receptor activator of NF-kappaB signaling pathways","volume":"283","author":"Yoshitake","year":"2008","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bone.2009.06.004_bib23","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/(SICI)1521-2254(200005\/06)2:3<194::AID-JGM102>3.0.CO;2-5","article-title":"The role of IL-6 in the inflammatory and humoral response to adenoviral vectors","volume":"2","author":"Benihoud","year":"2000","journal-title":"J. Gene Med."},{"key":"10.1016\/j.bone.2009.06.004_bib24","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/368339a0","article-title":"Impaired immune and acute-phase responses in interleukin-6-deficient mice","volume":"368","author":"Kopf","year":"1994","journal-title":"Nature"},{"key":"10.1016\/j.bone.2009.06.004_bib25","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1002\/j.1460-2075.1994.tb06368.x","article-title":"Interleukin-6 deficient mice are protected from bone loss caused by estrogen depletion","volume":"13","author":"Poli","year":"1994","journal-title":"EMBO J."},{"key":"10.1016\/j.bone.2009.06.004_bib26","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1002\/jor.1100180602","article-title":"Quantitative small-animal surrogate to evaluate drug efficacy in preventing wear debris-induced osteolysis","volume":"18","author":"Schwarz","year":"2000","journal-title":"J. Orthop. Res."},{"key":"10.1016\/j.bone.2009.06.004_bib27","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1002\/j.1460-2075.1991.tb04978.x","article-title":"Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis","volume":"10","author":"Keffer","year":"1991","journal-title":"EMBO J."},{"key":"10.1016\/j.bone.2009.06.004_bib28","doi-asserted-by":"crossref","first-page":"R49","DOI":"10.1186\/ar612","article-title":"Exposure to receptor\u2013activator of NFkappaB ligand renders pre-osteoclasts resistant to IFN-gamma by inducing terminal differentiation","volume":"5","author":"Huang","year":"2003","journal-title":"Arthritis Res. Ther."},{"key":"10.1016\/j.bone.2009.06.004_bib29","doi-asserted-by":"crossref","first-page":"5990","DOI":"10.4049\/jimmunol.164.11.5990","article-title":"NF-kappa B regulates VCAM-1 expression on fibroblast-like synoviocytes","volume":"164","author":"Li","year":"2000","journal-title":"J. Immunol."},{"key":"10.1016\/j.bone.2009.06.004_bib30","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/S0736-0266(01)00180-2","article-title":"The role of p105 protein in NFkappaB activation in ANA-1 murine macrophages following stimulation with titanium particles","volume":"20","author":"Soloviev","year":"2002","journal-title":"J. Orthop. Res."},{"issue":"Suppl. 2","key":"10.1016\/j.bone.2009.06.004_bib31","doi-asserted-by":"crossref","first-page":"ii82","DOI":"10.1136\/ard.61.suppl_2.ii82","article-title":"Tumour necrosis factor superfamily cytokines and the pathogenesis of inflammatory osteolysis","volume":"61","author":"Lam","year":"2002","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.bone.2009.06.004_bib32","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.intimp.2004.03.004","article-title":"Administration of macrophage colony-stimulating factor mobilized both CD11b+CD11c+ cells and NK1.1+ cells into peripheral blood","volume":"4","author":"Misawa","year":"2004","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.bone.2009.06.004_bib33","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1210\/endo-128-5-2657","article-title":"Chinese hamster ovarian cells transfected with the murine interleukin-6 gene cause hypercalcemia as well as cachexia, leukocytosis and thrombocytosis in tumor-bearing nude mice","volume":"128","author":"Black","year":"1991","journal-title":"Endocrinology"},{"key":"10.1016\/j.bone.2009.06.004_bib34","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S8756-3282(98)00172-0","article-title":"Effect of interleukin-6 secreted by engineered human stromal cells on osteoclasts in human bone","volume":"24","author":"Sandhu","year":"1999","journal-title":"Bone"},{"key":"10.1016\/j.bone.2009.06.004_bib35","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.4049\/jimmunol.169.6.3353","article-title":"IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-kappa B ligand, osteoprotegerin, and receptor activator of NF-kappa B in mouse calvariae","volume":"169","author":"Palmqvist","year":"2002","journal-title":"J. Immunol."},{"key":"10.1016\/j.bone.2009.06.004_bib36","first-page":"1682","article-title":"Bone marrow neutrophilia and suppressed bone turnover in human interleukin-6 transgenic mice. A cellular relationship among hematopoietic cells, osteoblasts, and osteoclasts mediated by stromal cells in bone marrow","volume":"147","author":"Kitamura","year":"1995","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.bone.2009.06.004_bib37","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/1043-4666(90)90019-P","article-title":"IL 3 and IL 6 do not induce bone resorption in vitro","volume":"2","author":"Barton","year":"1990","journal-title":"Cytokine"},{"key":"10.1016\/j.bone.2009.06.004_bib38","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/BF00297186","article-title":"Interleukin-6 does not mediate the stimulation by prostaglandin E2, parathyroid hormone, or 1,25 dihydroxyvitamin D3 of osteoclast differentiation and bone resorption in neonatal mouse parietal bones","volume":"55","author":"Holt","year":"1994","journal-title":"Calcif. Tissue Int."},{"key":"10.1016\/j.bone.2009.06.004_bib39","doi-asserted-by":"crossref","first-page":"3688","DOI":"10.1210\/en.2007-1719","article-title":"Interleukin-6 inhibits receptor activator of nuclear factor kappaB ligand-induced osteoclastogenesis by diverting cells into the macrophage lineage: key role of Serine727 phosphorylation of signal transducer and activator of transcription 3","volume":"149","author":"Duplomb","year":"2008","journal-title":"Endocrinology"},{"key":"10.1016\/j.bone.2009.06.004_bib40","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1136\/ard.2006.068064","article-title":"Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an X ray reader-blinded randomised controlled trial of tocilizumab","volume":"66","author":"Nishimoto","year":"2007","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.bone.2009.06.004_bib41","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S0140-6736(08)60453-5","article-title":"Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial","volume":"371","author":"Smolen","year":"2008","journal-title":"Lancet"},{"key":"10.1016\/j.bone.2009.06.004_bib42","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.yexmp.2008.03.003","article-title":"Early effects of tocilizumab on bone and bone marrow lesions in a collagen-induced arthritis monkey model","volume":"84","author":"Kato","year":"2008","journal-title":"Exp. Mol. Pathol."},{"key":"10.1016\/j.bone.2009.06.004_bib43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10254-003-0012-2","article-title":"IL-6 signal transduction and its physiological roles: the signal orchestration model","volume":"149","author":"Kamimura","year":"2003","journal-title":"Rev. Physiol. Biochem. Pharmacol."},{"key":"10.1016\/j.bone.2009.06.004_bib44","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1007\/s00223-003-0059-8","article-title":"A rapid multiparameter approach to study factors that regulate osteoclastogenesis: demonstration of the combinatorial dominant effects of TNF-alpha and TGF-ss in RANKL-mediated osteoclastogenesis","volume":"73","author":"Huang","year":"2003","journal-title":"Calcif. Tissue Int."},{"key":"10.1016\/j.bone.2009.06.004_bib45","first-page":"177","article-title":"Interleukin-6 reduces cartilage destruction during experimental arthritis. A study in interleukin-6-deficient mice","volume":"151","author":"van de Loo","year":"1997","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.bone.2009.06.004_bib46","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1210\/en.2003-0839","article-title":"Gp130-mediated signaling is necessary for normal osteoblastic function in vivo and in vitro","volume":"145","author":"Shin","year":"2004","journal-title":"Endocrinology"},{"key":"10.1016\/j.bone.2009.06.004_bib47","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1084\/jem.180.4.1243","article-title":"Defective inflammatory response in interleukin 6-deficient mice","volume":"180","author":"Fattori","year":"1994","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.bone.2009.06.004_bib48","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.4049\/jimmunol.146.7.2316","article-title":"Endotoxin-induced cytokine gene expression in vivo. III. IL-6 mRNA and serum protein expression and the in vivo hematologic effects of IL-6","volume":"146","author":"Ulich","year":"1991","journal-title":"J. Immunol."},{"key":"10.1016\/j.bone.2009.06.004_bib49","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1172\/JCI1368","article-title":"IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses","volume":"101","author":"Xing","year":"1998","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.bone.2009.06.004_bib50","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1182\/blood-2002-11-3437","article-title":"IL-4 suppresses osteoclast development and mature osteoclast function by a STAT6-dependent mechanism: irreversible inhibition of the differentiation program activated by RANKL","volume":"102","author":"Moreno","year":"2003","journal-title":"Blood"},{"key":"10.1016\/j.bone.2009.06.004_bib51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj20030407","article-title":"Principles of interleukin (IL)-6-type cytokine signalling and its regulation","volume":"374","author":"Heinrich","year":"2003","journal-title":"Biochem. J."},{"key":"10.1016\/j.bone.2009.06.004_bib52","doi-asserted-by":"crossref","first-page":"788","DOI":"10.2106\/JBJS.E.00711","article-title":"Wear debris inhibition of anti-osteoclastogenic signaling by interleukin-6 and interferon-gamma. Mechanistic insights and implications for periprosthetic osteolysis","volume":"88","author":"Rakshit","year":"2006","journal-title":"J. Bone Joint. Surg. Am."}],"container-title":["Bone"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S8756328209016287?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S8756328209016287?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T17:26:25Z","timestamp":1685035585000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S8756328209016287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,10]]},"references-count":52,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,10]]}},"alternative-id":["S8756328209016287"],"URL":"https:\/\/doi.org\/10.1016\/j.bone.2009.06.004","relation":{},"ISSN":["8756-3282"],"issn-type":[{"value":"8756-3282","type":"print"}],"subject":[],"published":{"date-parts":[[2009,10]]}}}