Abstract
TNFα is a potent osteoclastogenic cytokine that has a fundamental role in the pathogenesis of wear particle-induced osteolysis. Wear particles of one composition and their biological effects are well characterised. In contrast, little is known about the effects of mixed particles with respect to mix ratio and particle concentration. We evaluated the effects of different mix ratios of polyethylene and TiAlV particles on TNFα response. We used a human monocytic cell line (THP-1) in this in vitro study. THP-1 monocytes were differentiated to macrophage-like cells and exposed to different mixtures of lipopolysaccharide-detoxified polyethylene and TiAlV particles. TNFα was analysed in culture supernatants using ELISAs. Both polyethylene and TiAlV particles induced a dose- and time-related release of TNFα, with maximum levels after 6 h. A PE/TiAlV mix ratio of 36:1 at 108 particles/ml induced significantly higher TNFα concentrations compared to equal particle concentrations of isolated TiAlV (p=0.047) or PE (p=0.044), indicating the synergistic effect of mixed particles. These results provide evidence that TiAlV and polyethylene particles have significant synergistic effects, depending on the mix ratio and particle concentrations. This supra-additive effect can contribute substantially to the pathogenesis of implant particle-induced osteolysis.
Zusammenfassung
TNFα ist ein potentes, die Osteoklastogenese-stimulierendes Zytokin, das eine fundamentale Rolle in der Pathogenese von abriebpartikelinduzierten Osteolysen spielt. Dabei sind Abriebpartikel eines bestimmten Materials und deren biologische Effekte gut charakterisiert. Im Gegensatz dazu ist über die Effekte von gemischten Partikeln unter Berücksichtigung des Mischungsverhältnisses und der Partikelkonzentration wenig bekannt. Wir untersuchten die Effekte unterschiedlicher Mischungsverhältnisse von Polyethylen- und TiAlV-Partikel auf die TNFα-Antwort. In dieser in vitro-Studie verwendeten wir eine humane monozytäre Zelllinie (THP-1). Die Zellen wurden zu makrophagenähnlichen Zellen differenziert und unterschiedlichen Mixturen von LPS-detoxifizierten Polyethylen- und TiAlV-Partikeln ausgesetzt. TNFα wurde im Überstand mittels ELISA bestimmt. Sowohl Polyethylen als auch TiAlV-Partikel induzierten eine dosis- und zeitabhängige Freisetzung von TNFα mit einem signifikanten Maximum nach 6 Stunden. Das Mischungsverhältinis von PE/TiAlV 36:1 bei 108 Partikel/ml induzierte signifikant höhere TNFα-Konzentrationen im Vergleich zu gleichen Konzentrationen isolierter TiAlV- (p=0,047) oder PE-Partikel (p=0,044), was den synergistischen Effekt von Partikelmixturen verdeutlicht. Die Ergebnisse liefern Beweiskraft, dass TiAlV- und Polyethylenpartikel signifikante synergistische Effekte in Abhängigkeit von Mischungsverhältnissen und Partikelkonzentrationen haben. Dieser supraadditive Effekt kann substanziell der Pathogenese der abriebpartikelinduzierten Osteolyse zugeordnet werden.
References
1 Akisue T, Bauer TW, Farver CF, Mochida Y. The effect of particle wear debris on NF-κB activation and pro-inflammatory cytokine release in differentiated THP-1 cells. J Biomed Mater Res2002; 59: 507–515.10.1002/jbm.1264Search in Google Scholar
2 Aspenberg P, Van der Vis H. Migration, particles, and fluid pressure. A discussion of causes of prosthetic loosening. Clin Orthop Relat Res1998; 352: 75–80.10.1097/00003086-199807000-00010Search in Google Scholar
3 Auwerx J. The human leukemia cell line, THP-1: a multifaceted model for the study of monocyte-macrophage differentiation. Experientia1991; 47: 22–31.10.1007/BF02041244Search in Google Scholar
4 Baqui AA, Meiller TF, Chon JJ, Turng BF, Falkler WA Jr. Granulocyte-macrophage colony-stimulating factor amplification of interleukin-1β and tumor necrosis factor α production in THP-1 human monocytic cells stimulated with lipopolysaccharide of oral microorganisms. Clin Diagn Lab Immunol1998; 5: 341–347.10.1128/CDLI.5.3.341-347.1998Search in Google Scholar
5 Bauer TW. Particles and periimplant bone resorption. Clin Orthop Relat Res2002; 405: 138–143.10.1097/00003086-200212000-00016Search in Google Scholar
6 Baumann B, Rader CP, Seufert J, et al. Effects of polyethylene and TiAlV wear particles on expression of RANK, RANKL and OPG mRNA. Acta Orthop Scand2004; 75: 295–302.10.1080/00016470410001222Search in Google Scholar
7 Baumann B, Seufert J, Jakob F, et al. Activation of NF-κB signalling and TNFα expression in THP-1 macrophages by TiAlV and polyethylene wear particles. J Orthop Res2005; 23: 1241–1248.10.1016/j.orthres.2005.02.017Search in Google Scholar
8 Bi Y, Collier TO, Goldberg VM, Anderson JM, Greenfield EM. Adherent endotoxin mediates biological responses of titanium particles without stimulating their phagocytosis. J Orthop Res2002; 20: 696–703.10.1016/S0736-0266(01)00176-0Search in Google Scholar
9 Bi Y, Seabold JM, Kaar SG, et al. Adherent endotoxin on orthopedic wear particles stimulates cytokine production and osteoclast differentiation. J Bone Miner Res2001; 16: 2082–2091.10.1359/jbmr.2001.16.11.2082Search in Google Scholar PubMed
10 Boltz-Nitulescu G, Willheim M, Spittler A, Leutmezer F, Tempfer C, Winkler S. Modulation of IgA, IgE, and IgG Fc receptor expression on human mononuclear phagocytes by 1 α,25-dihydroxyvitamin D3 and cytokines. J Leukoc Biol1995; 58: 256–262.10.1002/jlb.58.2.256Search in Google Scholar PubMed
11 Chiang CY, Kyritsis G, Graves DT, Amar S. Interleukin-1 and tumor necrosis factor activities partially account for calvarial bone resorption induced by local injection of lipopolysaccharide. Infect Immun1999; 67: 4231–4236.10.1128/IAI.67.8.4231-4236.1999Search in Google Scholar
12 Childs LM, Goater JJ, O'Keefe RJ, Schwarz EM. Efficacy of Etanercept for wear debris-induced osteolysis. J Bone Miner Res2001; 16: 338–347.10.1359/jbmr.2001.16.2.338Search in Google Scholar
13 Choi MG, Koh HS, Kluess D, et al. Effects of titanium particle size on osteoblast functions in vitro and in vivo. Proc Natl Acad Sci USA2005; 102: 4578–4583.10.1073/pnas.0500693102Search in Google Scholar
14 Doorn PF, Campbell PA, Amstutz HC. Metal versus polyethylene wear particles in total hip replacements. A review. Clin Orthop Relat Res1996; 329 (Suppl): S206–S216.10.1097/00003086-199608001-00018Search in Google Scholar
15 Fornasier VL, Goodman SB, Protzner K, Kamel M, Song Y, Shojaci A. The role of implant alignment on stability and particles on periprosthetic osteolysis – a rabbit model of implant failure. J Biomed Mater Res B Appl Biomater2004; 70: 179–186.10.1002/jbm.b.20038Search in Google Scholar
16 Fujishiro T, Nishikawa T, Shibanuma N, et al. Effect of cyclic mechanical stretch and titanium particles on prostaglandin E2 production by human macrophages in vitro. J Biomed Mater Res2004; 68A: 531–536.10.1002/jbm.a.20098Search in Google Scholar
17 Gonzalez O, Smith RL, Goodman SB. Effect of size, concentration, surface area, and volume of polymethylmethacrylate particles on human macrophages in vitro. J Biomed Mater Res1996; 30: 463–473.10.1002/(SICI)1097-4636(199604)30:4<463::AID-JBM4>3.0.CO;2-NSearch in Google Scholar
18 Goodman SB. The effects of micromotion and particulate materials on tissue differentiation. Bone chamber studies in rabbits. Acta Orthop Scand Suppl1994; 258: 1–43.10.3109/17453679409155227Search in Google Scholar
19 Green TR, Fisher J, Stone M, Wroblewski BM, Ingham E. Polyethylene particles of a ‘critical size’ are necessary for the induction of cytokines by macrophages in vitro. Biomaterials1998; 19: 2297–2302.10.1016/S0142-9612(98)00140-9Search in Google Scholar
20 Harris WH. Conquest of a worldwide human disease: particle-induced periprosthetic osteolysis. Clin Orthop Relat Res2004; 429: 39–42.10.1097/01.blo.0000149821.72760.39Search in Google Scholar
21 Hirakawa K, Bauer TW, Stulberg BN, Wilde AH, Secic M. Characterization and comparison of wear debris from failed total hip implants of different types. J Bone Joint Surg Am1996; 78: 1235–1243.10.2106/00004623-199608000-00014Search in Google Scholar
22 Hirakawa K, Jacobs JJ, Urban R, Saito T. Mechanisms of failure of total hip replacements: lessons learned from retrieval studies. Clin Orthop Relat Res2004; 420: 10–17.10.1097/00003086-200403000-00003Search in Google Scholar
23 Howling GI, Barnett PI, Tipper JL, Stone MH, Fisher J, Ingham E. Quantitative characterization of polyethylene debris isolated from periprosthetic tissue in early failure knee implants and early and late failure Charnley hip implants. J Biomed Mater Res2001; 58: 415–420.10.1002/jbm.1036Search in Google Scholar
24 Huang CH, Ho FY, Ma HM, et al. Particle size and morphology of UHMWPE wear debris in failed total knee arthroplasties – a comparison between mobile bearing and fixed bearing knees. J Orthop Res2002; 20: 1038–1041.10.1016/S0736-0266(02)00015-3Search in Google Scholar
25 Jakob F, Siggelkow H, Homann D, Kohrle J, Adamski J, Schutze N. Local estradiol metabolism in osteoblast- and osteoclast-like cells. J Steroid Biochem Mol Biol1997; 61: 167–174.10.1016/S0960-0760(97)80009-XSearch in Google Scholar
26 Kadoya Y, Revell PA, Kobayashi A, Al Saffar N, Scott G, Freeman MA. Wear particulate species and bone loss in failed total joint arthroplasties. Clin Orthop Relat Res1997; 340: 118–129.10.1097/00003086-199707000-00016Search in Google Scholar
27 Lee JM, Salvati EA, Betts F, DiCarlo EF, Doty SB, Bullough PG. Size of metallic and polyethylene debris particles in failed cemented total hip replacements. J Bone Joint Surg Br1992; 74: 380–384.10.1302/0301-620X.74B3.1587882Search in Google Scholar
28 Maloney WJ, Smith RL, Schmalzried TP, Chiba J, Huene D, Rubash H. Isolation and characterization of wear particles generated in patients who have had failure of a hip arthroplasty without cement. J Bone Joint Surg Am1995; 77: 1301–1310.10.2106/00004623-199509000-00002Search in Google Scholar
29 Margevicius KJ, Bauer TW, McMahon JT, Brown SA, Merritt K. Isolation and characterization of debris in membranes around total joint prostheses. J Bone Joint Surg Am1994; 76: 1664–1675.10.2106/00004623-199411000-00010Search in Google Scholar
30 Matthews JB, Besong AA, Green TR, et al. Evaluation of the response of primary human peripheral blood mononuclear phagocytes to challenge with in vitro generated clinically relevant UHMWPE particles of known size and dose. J Biomed Mater Res2000; 52: 296–307.10.1002/1097-4636(200011)52:2<296::AID-JBM8>3.0.CO;2-9Search in Google Scholar
31 Merkel KD, Erdmann JM, McHugh KP, Abu-Amer Y, Ross FP, Teitelbaum SL. Tumor necrosis factor-α mediates orthopedic implant osteolysis. Am J Pathol1999; 154: 203–210.10.1016/S0002-9440(10)65266-2Search in Google Scholar
32 Mochida Y, Bauer TW, Koshino T, Hirakawa K, Saito T. Histologic and quantitative wear particle analyses of tissue around cementless ceramic total knee prostheses. J Arthroplasty2002; 17: 121–128.10.1054/arth.2002.29330Search in Google Scholar
33 Nakashima Y, Sun DH, Trindade MC, et al. Signaling pathways for tumor necrosis factor-α and interleukin-6 expression in human macrophages exposed to titanium-alloy particulate debris in vitro. J Bone Joint Surg Am1999; 81: 603–615.10.2106/00004623-199905000-00002Search in Google Scholar
34 Rader CP, Sterner T, Jakob F, Schutze N, Eulert J. Cytokine response of human macrophage-like cells after contact with polyethylene and pure titanium particles. J Arthroplasty1999; 14: 840–848.10.1016/S0883-5403(99)90035-9Search in Google Scholar
35 Ragab AA, Van De MR, Lavish SA, et al. Measurement and removal of adherent endotoxin from titanium particles and implant surfaces. J Orthop Res1999; 17: 803–809.10.1002/jor.1100170603Search in Google Scholar
36 Ren W, Li XH, Chen BD, Wooley PH. Erythromycin inhibits wear debris-induced osteoclastogenesis by modulation of murine macrophage NF-κB activity. J Orthop Res2004; 22: 21–29.10.1016/S0736-0266(03)00130-XSearch in Google Scholar
37 Ren W, Wu B, Mayton L, Wooley PH. Polyethylene and methyl methacrylate particle-stimulated inflammatory tissue and macrophages up-regulate bone resorption in a murine neonatal calvaria in vitro organ system. J Orthop Res2002; 20: 1031–1037.10.1016/S0736-0266(02)00019-0Search in Google Scholar
38 Ren W, Yang SY, Fang HW, Hsu S, Wooley PH. Distinct gene expression of receptor activator of nuclear factor-κB and rank ligand in the inflammatory response to variant morphologies of UHMWPE particles. Biomaterials2003; 24: 4819–4826.10.1016/S0142-9612(03)00384-3Search in Google Scholar
39 Ren W, Yang SY, Wooley PH. A novel murine model of orthopaedic wear-debris associated osteolysis. Scand J Rheumatol2004; 33: 349–357.10.1080/03009740410005944Search in Google Scholar PubMed
40 Rogers SD, Howie DW, Graves SE, Pearcy MJ, Haynes DR. In vitro human monocyte response to wear particles of titanium alloy containing vanadium or niobium. J Bone Joint Surg Br1997; 79: 311–315.10.1302/0301-620X.79B2.0790311Search in Google Scholar
41 Sabokbar A, Kudo O, Athanasou NA. Two distinct cellular mechanisms of osteoclast formation and bone resorption in periprosthetic osteolysis. J Orthop Res2003; 21: 73–80.10.1016/S0736-0266(02)00106-7Search in Google Scholar
42 Schwarz EM, Lu AP, Goater JJ, et al. Tumor necrosis factor-α/nuclear transcription factor-κB signaling in periprosthetic osteolysis. J Orthop Res2000; 18: 472–480.10.1002/jor.1100180321Search in Google Scholar
43 Shanbhag AS, Jacobs JJ, Glant TT, Gilbert JL, Black J, Galante JO. Composition and morphology of wear debris in failed uncemented total hip replacement. J Bone Joint Surg Br1994; 76: 60–67.10.1302/0301-620X.76B1.8300684Search in Google Scholar
44 Soloviev A, Schwarz EM, Darowish M, O'Keefe RJ. Sphingomyelinase mediates macrophage activation by titanium particles independent of phagocytosis: a role for free radicals, NF-κB, and TNFα. J Orthop Res2005; 23: 1258–1265.10.1016/j.orthres.2005.03.019.1100230604Search in Google Scholar
45 Tipper JL, Ingham E, Hailey JL, et al. Quantitative analysis of polyethylene wear debris, wear rate and head damage in retrieved Charnley hip prostheses. J Mater Sci Mater Med2000; 11: 117–124.Search in Google Scholar
46 Tsuchiya S, Yamabe M, Yamaguchi Y, Kobayashi Y, Konno T, Tada K. Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer1980; 26: 171–176.10.1002/ijc.2910260208Search in Google Scholar
47 von Knoch M, Jewison DE, Sibonga JD, et al. The effectiveness of polyethylene versus titanium particles in inducing osteolysis in vivo. J Orthop Res2004; 22: 237–243.10.1016/j.orthres.2003.08.013Search in Google Scholar
48 Voronov I, Santerre JP, Hinek A, Callahan JW, Sandhu J, Boynton EL. Macrophage phagocytosis of polyethylene particulate in vitro. J Biomed Mater Res1998; 39: 40–51.10.1002/(SICI)1097-4636(199801)39:1<40::AID-JBM6>3.0.CO;2-ISearch in Google Scholar
49 Wang ML, Hauschka PV, Tuan RS, Steinbeck MJ. Exposure to particles stimulates superoxide production by human THP-1 macrophages and avian HD-11EM osteoclasts activated by tumor necrosis factor-α and PMA. J Arthroplasty2002; 17: 335–346.10.1054/arth.2002.30416Search in Google Scholar
50 Wang ML, Sharkey PF, Tuan RS. Particle bioreactivity and wear-mediated osteolysis. J Arthroplasty2004; 19: 1028–1038.10.1016/j.arth.2004.03.024Search in Google Scholar
51 Wooley PH, Morren R, Andary J, et al. Inflammatory responses to orthopaedic biomaterials in the murine air pouch. Biomaterials2002; 23: 517–526.10.1016/S0142-9612(01)00134-XSearch in Google Scholar
52 Yang SY, Nasser S, Markel DC, Robbins PD, Wooley PH. Human periprosthetic tissues implanted in severe combined immunodeficient mice respond to gene transfer of a cytokine inhibitor. J Bone Joint Surg Am2005; 87: 1088–1097.10.2106/JBJS.D.02052Search in Google Scholar PubMed
©2006 by Walter de Gruyter Berlin New York
