{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:35:25Z","timestamp":1761708925917},"reference-count":24,"publisher":"Bentham Science Publishers Ltd.","issue":"1","license":[{"start":{"date-parts":[[2013,10,18]],"date-time":"2013-10-18T00:00:00Z","timestamp":1382054400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"content-domain":{"domain":["openorthopaedicsjournal.com","benthamopen.com"],"crossmark-restriction":true},"short-container-title":["TOORTHJ"],"published-print":{"date-parts":[[2013,10,18]]},"abstract":"<jats:p>Long-term aseptic failures of joint replacements are generally attributed to implant debris-induced inflammation and osteolysis. This response is largely mediated by immune and bone cells (monocytes\/macrophages and osteoclasts, respectively), that in the presence of implant debris (e.g. metal particles and ions), release pro-inflammatory cytokines such as IL-1\u03b2, TNF-\u03b1, and IL-6. The relative degree to which implant debris can illicit inflammatory response(s) from osteoclasts vs monocytes\/macrophages is unknown, i.e. are osteoclasts a viable target for anti-inflammatory therapy for implant debris? We investigated relative monocyte versus osteoclast inflammatory responses in a side-by-side comparison using implant debris from the perspective of both danger signaling (IL-1\u03b2) and pathogenic recognition (TNF-\u03b1) reactivity (Challenge Agents: Cobalt-alloy, Titanium-alloy, and PMMA particles, 0.9-1.8um-dia ECD and Cobalt, and Nickel-ions 0.01-0.1mM, all with and without LPS priming). Human monocytes\/macrophages reacted to implant debris with &gt;100 fold greater production of cytokines compared to osteoclast-like cells. Particulate Co-alloy challenge induced &gt;1000 pg\/ml of IL-1\u03b2 and TNF-\u03b1, in monocytes and &lt;50pg\/mL IL-1\u03b2 and TNF-\u03b1 in osteoclasts. Cobalt ions induced &gt;3000pg\/mL IL-1\u03b2 and TNF-\u03b1 in monocytes\/macrophages and &lt;50pg\/mL IL-1\u03b2 and TNF-\u03b1 in osteoclasts. The paracrine effect of supernatants from debris-treated monocytes\/macrophages was capable of inducing greater osteoclastogenesis (TRAP+, p&lt;0.06) and inflammation than direct debris challenge on osteoclasts. Our results indicate that as monocytes\/macrophages differentiate into osteoclasts, they largely lose their innate immune reactivity to implant debris and thus may not be as relevant a therapeutic target as monocytes\/macrophages for mitigating debris-induced inflammation.<\/jats:p>","DOI":"10.2174\/1874325001307010605","type":"journal-article","created":{"date-parts":[[2013,10,30]],"date-time":"2013-10-30T10:13:09Z","timestamp":1383127989000},"page":"605-613","update-policy":"http:\/\/dx.doi.org\/10.2174\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Osteoclasts Lose Innate Inflammatory Reactivity to Metal and Polymer Implant Debris Compared to Monocytes\/Macrophages"],"prefix":"10.2174","volume":"7","author":[{"given":"Jessica","family":"Yadav","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauryn","family":"Samelko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phil","family":"Gilvar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyron","family":"McAllister","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadim James","family":"Hallab","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","reference":[{"key":"refR1","doi-asserted-by":"crossref","first-page":"780","DOI":"10.2106\/00004623-200704000-00012","volume":"89","author":"Kurtz S","year":"2007","unstructured":"Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030 J Bone Joint Surg Am 2007; 89 (4) : 780-5.","journal-title":"J Bone Joint Surg Am"},{"key":"refR2","first-page":"233","volume":"43","author":"Friedman RJ","year":"1994","unstructured":"Friedman RJ, Black J, Galante JO, Jacobs JJ, Skinner HB. Current concepts in orthopaedic biomaterials and implant fixation Instr Course Lect 1994; 43 : 233-55.","journal-title":"Instr Course Lect"},{"key":"refR3","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/jbm.b.30308","volume":"75","author":"Ingram JH","year":"2005","unstructured":"Ingram JH, Kowalski R, Fisher J, Ingham E. The osteolytic response of macrophages to challenge with particles of Simplex P, Endurance, Palacos R, and Vertebroplastic bone cement particles in vitro J Biomed Mater Res B Appl Biomater 2005; 75 (1) : 210-0.","journal-title":"J Biomed Mater Res B Appl Biomater"},{"key":"refR4","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1016\/0142-9612(96)00072-5","volume":"17","author":"Wang JY","year":"1996","unstructured":"Wang JY, Wicklund BH, Gustilo RB, Tsukayama DT. Titanium, chromium and cobalt ions modulate the release of bone-associated cytokines by human monocytes\/macrophages in vitro Biomater 1996; 17 (23) : 2233-40.","journal-title":"Biomater"},{"key":"refR5","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/jbm.b.30861","volume":"84","author":"Tamaki Y","year":"2008","unstructured":"Tamaki Y, Sasaki K, Sasaki A, et al. Enhanced osteolytic potential of monocytes\/macrophages derived from bone marrow after particle stimulation J Biomed Mater Res B Appl Biomater 2008; 84 (1) : 191-204.","journal-title":"J Biomed Mater Res B Appl Biomater"},{"key":"refR6","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.arth.2004.03.024","volume":"19","author":"Wang ML","year":"2004","unstructured":"Wang ML, Sharkey PF, Tuan RS. Particle bioreactivity and wear-mediated osteolysis J Arthroplasty 2004; 19 (8) : 1028-38.","journal-title":"J Arthroplasty"},{"key":"refR7","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0736-0266(03)00156-6","volume":"22","author":"Clohisy JC","year":"2004","unstructured":"Clohisy JC, Hirayama T, Frazier E, Han SK, Abu-Amer Y. NF-kB signaling blockade abolishes implant particle-induced osteoclastogenesis J Orthop Res 2004; 22 (1) : 13-20.","journal-title":"J Orthop Res"},{"key":"refR8","doi-asserted-by":"crossref","first-page":"3330","DOI":"10.1016\/j.molimm.2008.04.022","volume":"45","author":"Mormann M","year":"2008","unstructured":"Mormann M, Thederan M, Nackchbandi I, Giese T, Wagner C, Hansch GM. Lipopolysaccharides (LPS) induce the differentiation of human monocytes to osteoclasts in a tumour necrosis factor (TNF) alpha-dependent manner: a link between infection and pathological bone resorption Mol Immunol 2008; 45 (12) : 3330-7.","journal-title":"Mol Immunol"},{"key":"refR9","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.prp.2008.07.002","volume":"204","author":"Wei S","year":"2008","unstructured":"Wei S, Siegal GP. Mechanisms modulating inflammatory osteolysis: a review with insights into therapeutic targets Pathol Res Pract 2008; 204 (10) : 695-706.","journal-title":"Pathol Res Pract"},{"key":"refR10","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1006\/excr.1998.4320","volume":"247","author":"Jimi E","year":"1999","unstructured":"Jimi E, Nakamura I, Duong LT, et al. Interleukin 1 induces multinucleation and bone-resorbing activity of osteoclasts in the absence of osteoblasts\/stromal cells Exp Cell Res 1999; 247 (1) : 84-93.","journal-title":"Exp Cell Res"},{"key":"refR11","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.mehy.2010.10.023","volume":"76","author":"Liu YP","year":"2011","unstructured":"Liu YP, Yu GR, Li K, Yuan F. Is there another possible approach to inhibit wear particles-induced inflammatory osteolysis? Med Hypotheses 2011; 76 (2) : 280-.","journal-title":"Med Hypotheses"},{"key":"refR12","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1002\/1097-4636(200009)53:5<490::AID-JBM7>3.0.CO;2-7","volume":"53","author":"Green TR","year":"2000","unstructured":"Green TR, Fisher J, Matthews JB, Stone MH, Ingham E. Effect of size and dose on bone resorption activity of macrophages by in vitro clinically relevant ultra high molecular weight polyethylene particles J Biomed Mater Res 2000; 53 (5) : 490-7.","journal-title":"J Biomed Mater Res"},{"key":"refR13","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1002\/jor.20826","volume":"27","author":"Caicedo MS","year":"2008","unstructured":"Caicedo MS, Desai R, McAllister K, Reddy A, Jacobs JJ, Hallab NJ. Soluble and particulate Co-Cr-Mo alloy implant metals activate the inflammasome danger signaling pathway in human macrophages: A novel mechanism for implant debris reactivity J Orthop Res 2008; 27 (7) : 847-54.","journal-title":"J Orthop Res"},{"key":"refR14","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1002\/jcb.20197","volume":"93","author":"Abu-Amer Y","year":"2004","unstructured":"Abu-Amer Y, Abbas S, Hirayama T. TNF receptor type 1 regulates RANK ligand expression by stromal cells and modulates osteoclastogenesis J Cell Biochem 2004; 93 (5) : 980-.","journal-title":"J Cell Biochem"},{"key":"refR15","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/S0736-0266(02)00133-X","volume":"21","author":"Clohisy JC","year":"2003","unstructured":"Clohisy JC, Frazier E, Hirayama T, Abu-Amer Y. RANKL is an essential cytokine mediator of polymethylmethacrylate particle-induced osteoclastogenesis J Orthop Res 2003; 21 (2) : 202-12.","journal-title":"J Orthop Res"},{"key":"refR16","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1006\/cyto.2000.0753","volume":"12","author":"Stea S","year":"2000","unstructured":"Stea S, Visentin M, Granchi D, et al. Cytokines and osteolysis around total hip prostheses Cytokine 2000; 12 (10) : 1575-9.","journal-title":"Cytokine"},{"key":"refR17","doi-asserted-by":"crossref","first-page":"5926","DOI":"10.4049\/jimmunol.1001591","volume":"185","author":"Lee B","year":"2010","unstructured":"Lee B, Kim TH, Jun JB, et al. Direct inhibition of human RANK+ osteoclast precursors identifies a homeostatic function of IL-1beta J Immunol 2010; 185 (10) : 5926-34.","journal-title":"J Immunol"},{"key":"refR18","doi-asserted-by":"crossref","first-page":"3688","DOI":"10.4049\/jimmunol.170.7.3688","volume":"170","author":"Itoh K","year":"2003","unstructured":"Itoh K, Udagawa N, Kobayashi K, et al. Lipopolysaccharide promotes the survival of osteoclasts via Toll-like receptor 4, but cytokine production of osteoclasts in response to lipopolysaccharide is different from that of macrophages J Immunol 2003; 170 (7) : 3688-95.","journal-title":"J Immunol"},{"key":"refR19","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.bbrc.2007.06.023","volume":"360","author":"Islam S","year":"2007","unstructured":"Islam S, Hassan F, Tumurkhuu G, et al. Bacterial lipopolysaccharide induces osteoclast formation in RAW 264.7 macrophage cells Biochem Biophys Res Commun 2007; 360 (2) : 346-51.","journal-title":"Biochem Biophys Res Commun"},{"key":"refR20","doi-asserted-by":"crossref","first-page":"5535","DOI":"10.1016\/j.biomaterials.2011.04.046","volume":"32","author":"Pearl JI","year":"2011","unstructured":"Pearl JI, Ma T, Irani AR, Huang Z, et al. Role of the Toll-like receptor pathway in the recognition of orthopedic implant wear-debris particles Biomaterials 2011; 32 (24) : 5535-42.","journal-title":"Biomaterials"},{"key":"refR21","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.biomaterials.2004.04.035","volume":"26","author":"Ingham E","year":"2005","unstructured":"Ingham E, Fisher J. The role of macrophages in osteolysis of total joint replacement Biomaterials 2005; 26 (11) : 1271-86.","journal-title":"Biomaterials"},{"key":"refR22","doi-asserted-by":"crossref","first-page":"501","DOI":"10.2106\/00004623-200104000-00004","volume":"83-A","author":"Bi Y","year":"2001","unstructured":"Bi Y, Van De Motter RR, Ragab AA, Goldberg VM, Anderson JM, Greenfield EM. Titanium particles stimulate bone resorption by inducing differentiation of murine osteoclasts J Bone Joint Surg Am 2001; 83-A (4) : 501-8.","journal-title":"J Bone Joint Surg Am"},{"key":"refR23","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/jbm.a.32183","volume":"91","author":"Cadosch D","year":"2009","unstructured":"Cadosch D, Chan E, Gautschi OP, Meagher J, Zellweger R, Filgueira L. Titanium IV ions induced human osteoclast differentiation and enhanced bone resorption in vitro J Biomed Mater Res A 2009; 91 (1) : 29-36.","journal-title":"J Biomed Mater Res A"},{"key":"refR24","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.bone.2011.06.007","volume":"49","author":"Andrews RE","year":"2011","unstructured":"Andrews RE, Shah KM, Wilkinson JM, Gartland A. Effects of cobalt and chromium ions at clinically equivalent concentrations after metal-on-metal hip replacement on human osteoblasts and osteoclasts: implications for skeletal health Bone 2011; 49 (4) : 717-23.","journal-title":"Bone"}],"container-title":["The Open Orthopaedics Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/openorthopaedicsjournal.com\/contents\/volumes\/V7\/TOORTHJ-7-605\/TOORTHJ-7-605.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openorthopaedicsjournal.com\/contents\/volumes\/V7\/TOORTHJ-7-605\/TOORTHJ-7-605.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openorthopaedicsjournal.com\/contents\/volumes\/V7\/TOORTHJ-7-605\/TOORTHJ-7-605.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T02:37:22Z","timestamp":1596767842000},"score":1,"resource":{"primary":{"URL":"https:\/\/openorthopaedicsjournal.com\/VOLUME\/7\/PAGE\/605\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,18]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,10,18]]}},"alternative-id":["TOORTHJ-7-605"],"URL":"https:\/\/doi.org\/10.2174\/1874325001307010605","relation":{},"ISSN":["1874-3250"],"issn-type":[{"value":"1874-3250","type":"print"}],"subject":[],"published":{"date-parts":[[2013,10,18]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2013-4-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-9-27","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-9-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-10-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}