Exposure to receptor-activator of NFκB ligand renders pre-osteoclasts resistant to IFN-γ by inducing terminal differentiation
Tóm tắt
While it has been established that IFN-γ is a strong activator of macrophages and a potent inhibitor of osteoclastogenesis in vitro, it is also known that this cytokine is produced in particular settings of inflammatory bone loss, such as infection and psoriatic arthritis. Because of the different kinetics between rapid IFN-γ macrophage activation (<24 hours) and the slower receptor-activator of NFκB ligand (RANKL) osteoclast differentiation (7 days), we postulated that IFN-γ would have different effects on early-stage and late-stage osteoclast precursors. In RAW264.7 cells and primary splenocyte cultures, pretreatment with RANKL rendered these cells resistant to maximally anti-osteoclastogenic doses of IFN-γ. These cells were also resistant to IFN-γ-induced nitric oxide production, morphological change, and surface upregulation of CD11b and receptor-activator of NFκB, suggesting that early exposure of osteoclast precursors to RANKL induces a broad resistance to the cellular effects of IFN-γ. Changes in STAT1 activation did not correlate with this resistance, as IFN-γ activated STAT1 equally in both early-stage and late-stage pre-osteoclasts. Furthermore, we failed to observe changes in TRAF6 expression following IFN-γ treatment in pre-osteoclasts. Together these data support a model of inflammatory bone loss in which early exposure to RANKL can prime osteoclast precursors to form in the presence of high levels of IFN-γ using mechanisms independent of the signal molecules STAT1 and TRAF6.
Tài liệu tham khảo
Teitelbaum SL: Bone resorption by osteoclasts. Science. 2000, 289: 1504-1508. 10.1126/science.289.5484.1504.
Childs LM, Goater JJ, O'Keefe RJ, Schwarz EM: Efficacy of etanercept for wear debris-induced osteolysis. J Bone Miner Res. 2001, 16: 338-347.
Arthritis Foundation. [http://www.arthritis.org/Answers/Disease-Center/ra.asp]
Suda T, Kobayashi K, Jimi E, Udagawa N, Takahashi N: The molecular basis of osteoclast differentiation and activation. Novartis Found Symp. 2001, 232: 235-247. 10.1002/0470846658.ch16.
Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Boyle WJ, Riggs BL: The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res. 2000, 15: 2-12.
Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos AJ, Van G, Itie A, Khoo W, Wakeham A, Dunstan CR, Lacey DL, Mak TW, Boyle WJ, Penninger JM: OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999, 397: 315-323. 10.1038/16852.
Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998, 93: 165-176. 10.1016/S0092-8674(00)81569-X.
Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T: Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA. 1998, 95: 3597-3602. 10.1073/pnas.95.7.3597.
Lam J, Takeshita S, Barker JE, Kanagawa O, Ross FP, Teitelbaum SL: TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest. 2000, 106: 1481-1488.
Mundy GR: Cytokines and Bone Remodeling. 1996, San Diego, CA: Academic Press
Jimi E, Nakamura I, Duong LT, Ikebe T, Takahashi N, Rodan GA, Suda T: Interleukin 1 induces multinucleation and bone-resorbing activity of osteoclasts in the absence of osteoblasts/stromal cells. ExpCell Res. 1999, 247: 84-93. 10.1006/excr.1998.4320.
Horwood NJ, Elliott J, Martin TJ, Gillespie MT: IL-12 alone and in synergy with IL-18 inhibits osteoclast formation in vitro. J Immunol. 2001, 166: 4915-4921.
Hong MH, Williams H, Jin CH, Pike JW: The inhibitory effect of interleukin-10 on mouse osteoclast formation involves novel tyrosine-phosphorylated proteins. J Bone Miner Res. 2000, 15: 911-918.
Fox SW, Chambers TJ: Interferon-gamma directly inhibits TRANCE-induced osteoclastogenesis. Biochem Biophys Res Commun. 2000, 276: 868-872. 10.1006/bbrc.2000.3577.
Takahashi N, Mundy GR, Roodman GD: Recombinant human interferon-gamma inhibits formation of human osteoclast-like cells. J Immunol. 1986, 137: 3544-3549.
OMIM, interferon-gamma listing. NCBI [electronic citation]. 14 May 2002
Tau G, Rothman P: Biologic functions of the IFN-gamma receptors. Allergy. 1999, 54: 1233-1251. 10.1034/j.1398-9995.1999.00099.x.
Farrar MA, Schreiber RD: The molecular cell biology of interferon-gamma and its receptor. Annu Rev Immunol. 1993, 11: 571-611. 10.1146/annurev.iy.11.040193.003035.
Takahashi N, Udagawa N, Suda T: A new member of tumor necrosis factor ligand family, ODF/OPGL/TRANCE/RANKL, regulates osteoclast differentiation and function. Biochem Biophys Res Commun. 1999, 256: 449-455. 10.1006/bbrc.1999.0252.
Kong YY, Feige U, Sarosi I, Bolon B, Tafuri A, Morony S, Capparelli C, Li J, Elliott R, McCabe S, Wong T, Campagnuolo G, Moran E, Bogoch ER, Van G, Nguyen LT, Ohashi PS, Lacey DL, Fish E, Boyle WJ, Penninger JM: Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprote-gerin ligand. Nature. 1999, 402: 304-309. 10.1038/46303.
Vermeire K, Heremans H, Vandeputte M, Huang S, Billiau A, Matthys P: Accelerated collagen-induced arthritis in IFN-gamma receptor-deficient mice. J Immunol. 1997, 158: 5507-5513.
Manoury-Schwartz B, Chiocchia G, Bessis N, Abehsira-Amar O, Batteux F, Muller S, Huang S, Boissier MC, Fournier C: High susceptibility to collagen-induced arthritis in mice lacking IFN-gamma receptors. J Immunol. 1997, 158: 5501-5506.
Arnoldi J, Gerdes J, Flad HD: Immunohistologic assessment of cytokine production of infiltrating cells in various forms of leprosy. Am J Pathol. 1990, 137: 749-753.
Desai SD, Birdi TJ, Antia NH: Correlation between macrophage activation and bactericidal function and Mycobacterium leprae antigen presentation in macrophages of leprosy patients and normal individuals. Infect Immun. 1989, 57: 1311-1317.
Firestein GS, Alvaro-Gracia JM, Maki R, Alvaro-Garcia JM: Quantitative analysis of cytokine gene expression in rheumatoid arthritis. J Immunol. 1990, 144: 3347-3353.
Ritchlin C, Haas-Smith SA, Hicks D, Cappuccio J, Osterland CK, Looney RJ: Patterns of cytokine production in psoriatic synovium. J Rheumatol. 1998, 25: 1544-1552.
Park SH, Min DJ, Cho ML, Kim WU, Youn J, Park W, Cho CS, Kim HY: Shift toward T helper 1 cytokines by type II collagen-reactive T cells in patients with rheumatoid arthritis. Arthritis Rheum. 2001, 44: 561-569. 10.1002/1529-0131(200103)44:3<561::AID-ANR104>3.3.CO;2-Q.
Cannon GW, Pincus SH, Emkey RD, Denes A, Cohen SA, Wolfe F, Saway PA, Jaffer AM, Weaver AL, Cogen L: Double-blind trial of recombinant gamma-interferon versus placebo in the treatment of rheumatoid arthritis. Arthritis Rheum. 1989, 32: 964-973.
Veys EM, Mielants H, Verbruggen G, Grosclaude JP, Meyer W, Galazka A, Schindler J: Interferon gamma in rheumatoid arthritis – a double blind study comparing human recombinant interferon gamma with placebo. J Rheumatol. 1988, 15: 570-574.
Veys EM, Menkes CJ, Emery P: A randomized, double-blind study comparing twenty-four-week treatment with recombinant interferon-gamma versus placebo in the treatment of rheumatoid arthritis. Arthritis Rheum. 1997, 40: 62-68.
Key LL, Rodriguiz RM, Willi SM, Wright NM, Hatcher HC, Eyre DR, Cure JK, Griffin PP, Ries WL: Long-term treatment of osteopetrosis with recombinant human interferon gamma. N Engl J Med. 1995, 332: 1594-1599. 10.1056/NEJM199506153322402.
Lam J, Nelson CA, Ross FP, Teitelbaum SL, Fremont DH: Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity. J Clin Invest. 2001, 108: 971-979. 10.1172/JCI200113890.
Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D, Galibert L: A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature. 1997, 390: 175-179. 10.1038/36593.
Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms E, Tan HL, Elliott G, Kelley MJ, Sarosi I, Wang L, Xia XZ, Elliott R, Chiu L, Black T, Scully S, Capparelli C, Morony S, Shimamoto G, Bass MB, Boyle WJ: Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci USA. 1999, 96: 3540-3545. 10.1073/pnas.96.7.3540.
Lomaga MA, Yeh WC, Sarosi I, Duncan GS, Furlonger C, Ho A, Morony S, Capparelli C, Van G, Kaufman S, van der Heiden A, Itie A, Wakeham A, Khoo W, Sasaki T, Cao Z, Penninger JM, Paige CJ, Lacey DL, Dunstan CR, Boyle WJ, Goeddel DV, Mak TW: TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev. 1999, 13: 1015-1024.
Bach EA, Aguet M, Schreiber RD: The IFN gamma receptor: a paradigm for cytokine receptor signaling. Annu Rev Immunol. 1997, 15: 563-591. 10.1146/annurev.immunol.15.1.563.
Meraz MA, White JM, Sheehan KC, Bach EA, Rodig SJ, Dighe AS, Kaplan DH, Riley JK, Greenlund AC, Campbell D, Carver-Moore K, DuBois RN, Clark R, Aguet M, Schreiber RD: Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell. 1996, 84: 431-442. 10.1016/S0092-8674(00)81288-X.
Takayanagi H, Ogasawara K, Hida S, Chiba T, Murata S, Sato K, Takaoka A, Yokochi T, Oda H, Tanaka K, Nakamura K, Taniguchi T: T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma. Nature. 2000, 408: 600-605. 10.1038/35046102.
Canete JD, Martinez SE, Farres J, Sanmarti R, Blay M, Gomez A, Salvador G, Munoz-Gomez J: Differential Th1/Th2 cytokine patterns in chronic arthritis: interferon gamma is highly expressed in synovium of rheumatoid arthritis compared with seronegative spondyloarthropathies. Ann Rheum Dis. 2000, 59: 263-268. 10.1136/ard.59.4.263.
Horwood NJ, Kartsogiannis V, Quinn JM, Romas E, Martin TJ, Gillespie MT: Activated T lymphocytes support osteoclast formation in vitro. Biochem BiophysRes Commun. 1999, 265: 144-150. 10.1006/bbrc.1999.1623.
Quinn JM, Horwood NJ, Elliott J, Gillespie MT, Martin TJ: Fibroblastic stromal cells express receptor activator of NF-kappa B ligand and support osteoclast differentiation. J Bone Miner Res. 2000, 15: 1459-1466.
Udagawa N, Takahashi N, Jimi E, Matsuzaki K, Tsurukai T, Itoh K, Nakagawa N, Yasuda H, Goto M, Tsuda E, Higashio K, Gillespie MT, Martin TJ, Suda T: Osteoblasts/stromal cells stimulate osteoclast activation through expression of osteoclast differentiation factor/RANKL but not macrophage colony-stimulating factor: receptor activator of NF-kappa B ligand. Bone. 1999, 25: 517-523. 10.1016/S8756-3282(99)00210-0.
Haynes DR, Crotti TN, Loric M, Bain GI, Atkins GJ, Findlay DM: Osteoprotegerin and receptor activator of nuclear factor kappaB ligand (RANKL) regulate osteoclast formation by cells in the human rheumatoid arthritic joint. Rheumatology (Oxford). 2001, 40: 623-630. 10.1093/rheumatology/40.6.623.
Kotake S, Udagawa N, Hakoda M, Mogi M, Yano K, Tsuda E, Takahashi K, Furuya T, Ishiyama S, Kim KJ, Saito S, Nishikawa T, Takahashi N, Togari A, Tomatsu T, Suda T, Kamatani N: Activated human T cells directly induce osteoclastogenesis from human monocytes: possible role of T cells in bone destruction in rheumatoid arthritis patients. Arthritis Rheum. 2001, 44: 1003-1012. 10.1002/1529-0131(200105)44:5<1003::AID-ANR179>3.3.CO;2-R.
Weitzmann MN, Cenci S, Rifas L, Haug J, Dipersio J, Pacifici R: T cell activation induces human osteoclast formation via receptor activator of nuclear factor kappaB ligand-dependent and -independent mechanisms. J Bone Miner Res. 2001, 16: 328-337.
Kobayashi N, Kadono Y, Naito A, Matsumoto K, Yamamoto T, Tanaka S, Inoue J: Segregation of TRAF6-mediated signaling pathways clarifies its role in osteoclastogenesis. EMBO J. 2001, 20: 1271-1280. 10.1093/emboj/20.6.1271.
Yang S, Madyastha P, Ries W, Key LL: Characterization of interferon gamma receptors on osteoclasts: effect of interferon gamma on osteoclastic superoxide generation. J Cell Biochem. 2002, 84: 645-654. 10.1002/jcb.10074.abs.
Cappellen D, Luong-Nguyen NH, Bongiovanni S, Grenet O, Wanke C, Susa M: Transcriptional program of mouse osteoclast differentiation governed by the macrophage colony-stimulating factor and the ligand for the receptor activator of NFkappa B. J Biol Chem. 2002
Abu-Amer Y: IL-4 abrogates osteoclastogenesis through STAT6-dependent inhibition of NF-kappaB. J Clin Invest. 2001, 107: 1375-1385.
Wei S, Wang MW, Teitelbaum SL, Ross FP: Interleukin-4 reversibly inhibits osteoclastogenesis via inhibition of NF-{kappa}B and MAP kinase signaling. J Biol Chem. 2001, 21: 21-
Haanen JB, de Waal MR, Res PC, Kraakman EM, Ottenhoff TH, de Vries RR, Spits H: Selection of a human T helper type 1-like T cell subset by mycobacteria. J Exp Med. 1991, 174: 583-592. 10.1084/jem.174.3.583.
Boissier MC, Chiocchia G, Bessis N, Hajnal J, Garotta G, Nicoletti F, Fournier C: Biphasic effect of interferon-gamma in murine collagen-induced arthritis. Eur J Immunol. 1995, 25: 1184-1190.
Machold KP, Neumann K, Smolen JS: Recombinant human interferon gamma in the treatment of rheumatoid arthritis: double blind placebo controlled study. Ann Rheum Dis. 1992, 51: 1039-1043.
Ortmann RA, Shevach EM: Susceptibility to collagen-induced arthritis: cytokine-mediated regulation. Clin Immunol. 2001, 98: 109-118. 10.1006/clim.2000.4961.
Cottard V, Mulleman D, Bouille P, Mezzina M, Boissier MC, Bessis N: Adeno-associated virus-mediated delivery of IL-4 prevents collagen-induced arthritis. Gene Ther. 2000, 7: 1930-1939. 10.1038/sj.gt.3301324.
Lubberts E, Joosten LA, Chabaud M, van Den BL, Oppers B, Coenen-De Roo CJ, Richards CD, Miossec P, van Den Berg WB: IL-4 gene therapy for collagen arthritis suppresses synovial IL-17 and osteoprotegerin ligand and prevents bone erosion. J Clin Invest. 2000, 105: 1697-1710.
Watanabe S, Imagawa T, Boivin GP, Gao G, Wilson JM, Hirsch R: Adeno-associated virus mediates long-term gene transfer and delivery of chondroprotective IL-4 to murine synovium. Mol Ther. 2000, 2: 147-152. 10.1006/mthe.2000.0111.