Orthopedic wear debris mediated inflammatory osteolysis is mediated in part by NALP3 inflammasome activation

被引:77
作者
Burton, Lyndsey [1 ]
Paget, Daniel [1 ]
Binder, Nikolaus B. [1 ]
Bohnert, Krista [1 ]
Nestor, Bryan J. [1 ]
Sculco, Thomas P. [1 ]
Santambrogio, Laura [2 ]
Ross, F. Patrick [1 ]
Goldring, Steven R. [1 ]
Purdue, P. Edward [1 ]
机构
[1] Hosp Special Surg, New York, NY 10021 USA
[2] Albert Einstein Coll Med, Dept Pathol, New York, NY 10461 USA
关键词
NALP3; inflammasome; periprosthetic osteolysis; interleukin-1; ss; caspase-1; NECROSIS-FACTOR-ALPHA; PERIPHERAL-BLOOD MONOCYTES; TOTAL HIP-ARTHROPLASTY; PERIPROSTHETIC OSTEOLYSIS; IN-VITRO; HUMAN MACROPHAGES; JOINT PROSTHESES; PARTICLES; INTERLEUKIN-6; MECHANISM;
D O I
10.1002/jor.22190
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Activation of myeloid cells by orthopedic particulate debris is a key event in the pathogenesis of periprosthetic osteolysis and implant loosening after total joint replacement (TJR). Several lines of evidence implicate NACHT, LRR, and PYD domains-containing protein 3 (NALP3) inflammasome-mediated production of interleukin 1 beta (IL-1 beta) in the pathogenesis of clinical disorders ascribable to foreign particulate materials, including asbestos, silica, and urate crystals. Recent reports indicate that orthopedic polymer products and metallic particulates and ions may activate the same pathway. Here, we investigated the contribution of the NALP3 inflammasome to the pathogenesis of peri-implant osteolysis. Pharmaceutical and genetic perturbations of caspase-1 and inflammasome components were used to assess the role of the NALP3 inflammasome in IL-1 beta production and osteoclast formation by human monocytes and mouse macrophages in response to polymethylmethacrylate (PMMA) particle phagocytosis. The role of caspase-1 in a mouse calvarial model of particle-mediated osteolysis was assessed using mu CT. Phagocytosis of PMMA particles induces caspase-1 dependent release of IL-1 beta from human monocytes and mouse macrophages. Importantly, using macrophages from mice deficient in components of the NALP3 inflammasome, we show PMMA-induced IL-1 beta production is strictly dependent on these components. Mice lacking caspase-1, the sole effector of the NALP3 inflammasome, show reduced orthopedic wear particle-induced calvarial osteolysis compared to wild-type controls. Absence of NALP3 inflammasome components fails to alter osteoclast formation in vitro. Our findings identify the NALP3 inflammasome as a critical mediator of orthopedic wear-induced osteolysis and as a viable therapeutic target for the treatment of periprosthetic osteolysis. (c) 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:7380, 2012
引用
收藏
页码:73 / 80
页数:8
相关论文
共 43 条
  • [1] Increased levels of tumor necrosis factor-alpha and interleukin-6 protein and messenger RNA in human peripheral blood monocytes due to titanium particles
    Blaine, TA
    Rosier, RN
    Puzas, JE
    Looney, RJ
    Reynolds, PR
    Reynolds, SD
    OKeefe, RJ
    [J]. JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 1996, 78A (08) : 1181 - 1192
  • [2] 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
    Caicedo, Marco S.
    Desai, Ronak
    McAllister, Kyron
    Reddy, Anand
    Jacobs, Joshua J.
    Hallab, Nadim J.
    [J]. JOURNAL OF ORTHOPAEDIC RESEARCH, 2009, 27 (07) : 847 - 854
  • [3] The Nalp3 inflammasome is essential for the development of silicosis
    Cassel, Suzanne L.
    Eisenbarth, Stephanie C.
    Iyer, Shankar S.
    Sadler, Jeffrey J.
    Colegio, Oscar R.
    Tephly, Linda A.
    Carter, A. Brent
    Rothman, Paul B.
    Flavell, Richard A.
    Sutterwala, Fayyaz S.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (26) : 9035 - 9040
  • [4] Mediators of the inflammatory response to joint replacement devices
    Cobelli, Neil
    Scharf, Brian
    Crisi, Giovanna M.
    Hardin, John
    Santambrogio, Laura
    [J]. NATURE REVIEWS RHEUMATOLOGY, 2011, 7 (10) : 600 - 608
  • [5] Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica
    Dostert, Catherine
    Petrilli, Virginie
    Van Bruggen, Robin
    Steele, Chad
    Mossman, Brooke T.
    Tschopp, Jurg
    [J]. SCIENCE, 2008, 320 (5876) : 674 - 677
  • [6] A literature review of the association between wear rate and osteolysis in total hip arthroplasty
    Dumbleton, JH
    Manley, MT
    Edidin, AA
    [J]. JOURNAL OF ARTHROPLASTY, 2002, 17 (05) : 649 - 661
  • [7] Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants
    Eisenbarth, Stephanie C.
    Colegio, Oscar R.
    O'Connor, William, Jr.
    Sutterwala, Fayyaz S.
    Flavell, Richard A.
    [J]. NATURE, 2008, 453 (7198) : 1122 - U13
  • [8] Innate instruction of adaptive immunity revisited: the inflammasome
    Eisenbarth, Stephanie C.
    Flavell, Richard A.
    [J]. EMBO MOLECULAR MEDICINE, 2009, 1 (02) : 92 - 98
  • [9] Interleukin-1 modulates periprosthetic tissue formation in an intramedullary model of particle-induced inflammation
    Epstein, NJ
    Warme, BA
    Spanogle, J
    Ma, T
    Bragg, B
    Smith, RL
    Goodman, SB
    [J]. JOURNAL OF ORTHOPAEDIC RESEARCH, 2005, 23 (03) : 501 - 510
  • [10] Ferrari D, 1997, J IMMUNOL, V159, P1451