The Open Orthopaedics Journal

ISSN: ― Volume ,

Osteoclasts Lose Innate Inflammatory Reactivity to Metal and Polymer Implant Debris Compared to Monocytes/Macrophages

Jessica Yadav3, Lauryn Samelko1, 2, Phil Gilvar4, Kyron McAllister 1, Nadim James Hallab*, 1
1 Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA
2 Department of Immunology, Rush University Medical Center, Chicago, IL 60612, USA
3 Department of Bioengineering, University of Illinois in Chicago, Chicago, IL 60612, USA
4 Medical College, University of Illinois in Chicago, Chicago, IL 60612, USA


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-1β, TNF-α, 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-1β) and pathogenic recognition (TNF-α) 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 >100 fold greater production of cytokines compared to osteoclast-like cells. Particulate Co-alloy challenge induced >1000 pg/ml of IL-1β and TNF-α, in monocytes and <50pg/mL IL-1β and TNF-α in osteoclasts. Cobalt ions induced >3000pg/mL IL-1β and TNF-α in monocytes/macrophages and <50pg/mL IL-1β and TNF-α in osteoclasts. The paracrine effect of supernatants from debris-treated monocytes/macrophages was capable of inducing greater osteoclastogenesis (TRAP+, p<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.

Keywords: DAMP, innate, implant debris, immune, ions, metal, monocyte/macrophages, osteoclasts, PAMP, particles.

Article Information

Identifiers and Pagination:

Year: 2013
Volume: 7
First Page: 605
Last Page: 613
Publisher Id: TOORTHJ-7-605
DOI: 10.2174/1874325001307010605

Article History:

Received Date: 20/4/2013
Revision Received Date: 27/9/2013
Acceptance Date: 30/9/2013
Electronic publication date: 18/10/2013
Collection year: 2013

© Yadav et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Orthopedic Surgery, Rush University Medical Center, 1735 W Harrison MC107, Chicago, IL 60612, USA; Tel: 312-942-7079; Fax: 312-942-8828; E-mail:

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