• 1
    Christodoulou C, Choy EH. Joint inflammation and cytokine inhibition in rheumatoid arthritis. Clin Exp Med 2006; 6: 139.
  • 2
    O'Shea JJ. Targeting the Jak/STAT pathway for immunosuppression. Ann Rheum Dis 2004; 63 Suppl II: ii6771.
  • 3
    Meyer DM, Jesson MI, Li X, Elrick MM, Funckes-Shippy CL, Warner JD, et al. Anti-inflammatory activity and neutrophil reductions mediated by the JAK1/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis. J Inflamm (Lond) 2010; 7: 41.
  • 4
    Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, et al. A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 2008; 26: 12732.
  • 5
    Flanagan ME, Blumenkopf TA, Brissette WH, Brown MF, Casavant JM, Shang-Poa C, et al. Discovery of CP-690,550: a potent and selective Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases and organ transplant rejection. J Med Chem 2010; 53: 846884.
  • 6
    Ghoreschi K, Jesson MI, Li X, Lee JL, Ghosh S, Alsup JW, et al. Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). J Immunol 2011; 186: 423443.
  • 7
    West K. CP-690550, a JAK3 inhibitor as an immunosuppressant for the treatment of rheumatoid arthritis, transplant rejection, psoriasis and other immune-mediated disorders. Curr Opin Investig Drugs 2009; 10: 491504.
  • 8
    Kremer JM, Bloom BJ, Breedveld FC, Coombs JH, Fletcher MP, Gruben D, et al. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo [published erratum appears in Arthritis Rheum 2012;64:1487]. Arthritis Rheum 2009; 60: 1895905.
  • 9
    Borie DC, O'Shea JJ, Changelian PS. JAK3 inhibition, a viable new modality of immunosuppression for solid organ transplants. Trends Mol Med 2004; 10: 53241.
  • 10
    O'Shea JJ, Gadina M, Schreiber RD. Cytokine signaling in 2002: new surprises in the Jak/Stat pathway. Cell 2002; 109 Suppl: S1231.
  • 11
    Pesu M, Candotti F, Husa M, Hofmann SR, Notarangelo LD, O'Shea JJ. Jak3, severe combined immunodeficiency, and a new class of immunosuppressive drugs. Immunol Rev 2005; 203: 12742.
  • 12
    Milici AJ, Kudlacz EM, Audoly L, Zwillich S, Changelian P. Cartilage preservation by inhibition of Janus kinase 3 in two rodent models of rheumatoid arthritis. Arthritis Res Ther 2008; 10: R14.
  • 13
    Tanaka Y, Suzuki M, Nakamura H, Toyoizumi S, Zwillich SH, and the Tofacitinib Study Investigators. Phase II study of tofacitinib (CP-690,550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate. Arthritis Care Res (Hoboken) 2011; 63: 11508.
  • 14
    Van der Heijde D, Tanaka Y, Fleischmann R, Keystone EC, Kremer JM, Zerbini CA, et al, and the ORAL Scan investigators. Tofacitinib (CP-690,550), an oral Janus kinase inhibitor, in combination with methotrexate reduced the progression of structural damage in patients with rheumatoid arthritis: a 24-month phase 3 study [abstract]. Arthritis Rheum 2011; 63 Suppl: S10178.
  • 15
    Hegen M, Keith JC Jr, Collins M, Nickerson-Nutter CL. Utility of animal models for identification of potential therapeutics for rheumatoid arthritis. Ann Rheum Dis 2008; 67: 150515.
  • 16
    Magari K, Miyata S, Nishigaki F, Ohkubo Y, Mutoh S, Goto T. Differential effects of FK506 and methotrexate on inflammatory cytokine levels in rat adjuvant-induced arthritis. J Rheumatol 2003; 30: 2193200.
  • 17
    Bendele AM, McComb J, Gould T, Frazier J, Chlipala ES, Seely J, et al. Combination benefit of PEGylated soluble tumor necrosis factor receptor type I (PEG sTNF-RI) and dexamethasone or indomethacin in adjuvant arthritic rats. Inflamm Res 1999; 48: 45360.
  • 18
    Bendele A, McComb J, Gould T, McAbee T, Sennello G, Chlipala E, et al. Animal models of arthritis: relevance to human disease. Toxicol Pathol 1999; 27: 13442.
  • 19
    Lin TH, Hegen M, Quadros E, Nickerson-Nutter CL, Appell KC, Cole AG, et al. Selective functional inhibition of JAK-3 is sufficient for efficacy in collagen-induced arthritis in mice. Arthritis Rheum 2010; 62: 228393.
  • 20
    LaBranche TP, Hickman-Brecks CL, Meyer DM, Storer CE, Jesson MI, Shevlin KM, et al. Characterization of the KRN cell transfer model of rheumatoid arthritis (KRN-CTM), a chronic yet synchronized version of the K/BxN mouse. Am J Pathol 2010; 177: 138896.
  • 21
    Bendele AM, Chlipala ES, Scherrer J, Frazier J, Sennello G, Rich WJ, et al. Combination benefit of treatment with the cytokine inhibitors interleukin-1 receptor antagonist and PEGylated soluble tumor necrosis factor receptor type I in animal models of rheumatoid arthritis. Arthritis Rheum 2000; 43: 264859.
  • 22
    Marshak DR, Greenwalt DE. Differentiating primary human cells in rapid-throughput discovery applications. Methods Mol Biol 2007; 356: 1218.
  • 23
    Damoiseaux JG, Dopp EA, Calame W, Chao D, MacPherson GG, Dijkstra CD. Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1. Immunology 1994; 83: 1407.
  • 24
    Haringman JJ, Gerlag DM, Zwinderman AH, Smeets TJ, Kraan MC, Baeten D, et al. Synovial tissue macrophages: a sensitive biomarker for response to treatment in patients with rheumatoid arthritis. Ann Rheum Dis 2005; 64: 8348.
  • 25
    Wijbrandts CA, Vergunst CE, Haringman JJ, Gerlag DM, Smeets TJ, Tak PP. Absence of changes in the number of synovial sublining macrophages after ineffective treatment for rheumatoid arthritis: implications for use of synovial sublining macrophages as a biomarker. Arthritis Rheum 2007; 56: 386971.
  • 26
    Nicolls MR, Aversa GG, Pearce NW, Spinelli A, Berger MF, Gurley KE, et al. Induction of long-term specific tolerance to allografts in rats by therapy with an anti-CD3-like monoclonal antibody. Transplantation 1993; 55: 45968.
  • 27
    McComb J, Gould T, Chlipala E, Sennelo G, Frazier J, Kieft G, et al. Antiarthritic activity of soluble tumor necrosis factor receptor type I forms in adjuvant arthritis: correlation of plasma levels with efficacy. J Rheumatol 1999; 26: 134751.
  • 28
    Mbalaviele G, Anderson G, Jones A, De Ciechi P, Settle S, Mnich S, et al. Inhibition of p38 mitogen-activated protein kinase prevents inflammatory bone destruction. J Pharmacol Exp Ther 2006; 317: 104453.
  • 29
    Changelian PS, Flanagan ME, Ball DJ, Kent CR, Magnuson KS, Martin WH, et al. Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science 2003; 302: 8758.
  • 30
    Parganas E, Wang D, Stravopodis D, Topham DJ, Marine JC, Teglund S, et al. Jak2 is essential for signaling through a variety of cytokine receptors. Cell 1998; 93: 38595.
  • 31
    Skerry TM, Suva LJ. Investigation of the regulation of bone mass by mechanical loading: from quantitative cytochemistry to gene array. Cell Biochem Funct 2003; 21: 2239.
  • 32
    Blair HC, Athanasou NA. Recent advances in osteoclast biology and pathological bone resorption. Histol Histopathol 2004; 19: 18999.
  • 33
    Radi ZA, Guzman RE, Bell RR. Increased connective tissue extracellular matrix in the op/op model of osteopetrosis. Pathobiology 2009; 76: 199203.
  • 34
    Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 1998; 95: 3597602.
  • 35
    Teitelbaum SL. Bone resorption by osteoclasts. Science 2000; 289: 15048.
  • 36
    Wong PK, Quinn JM, Sims NA, van Nieuwenhuijze A, Campbell IK, Wicks IP. Interleukin-6 modulates production of T lymphocyte–derived cytokines in antigen-induced arthritis and drives inflammation-induced osteoclastogenesis. Arthritis Rheum 2006; 54: 15868.
  • 37
    Horwood N. Lymphocyte-derived cytokines in inflammatory arthritis. Autoimmunity 2008; 41: 2308.
  • 38
    Poubelle PE, Chakravarti A, Fernandes MJ, Doiron K, Marceau AA. Differential expression of RANK, RANK-L, and osteoprotegerin by synovial fluid neutrophils from patients with rheumatoid arthritis and by healthy human blood neutrophils. Arthritis Res Ther 2007; 9: R25.
  • 39
    Yeo L, Toellner KM, Salmon M, Filer A, Buckley CD, Raza K, et al. Cytokine mRNA profiling identifies B cells as a major source of RANKL in rheumatoid arthritis. Ann Rheum Dis 2011; 70: 20228.
  • 40
    Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009; 361: 75665.
  • 41
    Djaafar S, Pierroz DD, Chicheportiche R, Zheng XX, Ferrari SL, Ferrari-Lacraz S. Inhibition of T cell–dependent and RANKL-dependent osteoclastogenic processes associated with high levels of bone mass in interleukin-15 receptor–deficient mice. Arthritis Rheum 2010; 62: 330010.
  • 42
    Weitzmann MN, Cenci S, Rifas L, Brown C, Pacifici R. Interleukin- 7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines. Blood 2000; 96: 18738.
  • 43
    Kwok SK, Cho ML, Park MK, Oh HJ, Park JS, Her YM, et al. Interleukin-21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen-induced arthritis. Arthritis Rheum 2012; 64: 74051.
  • 44
    Takayanagi H, Ogasawara K, Hida S, Chiba T, Murata S, Sato K, et al. T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-γ. Nature 2000; 408: 6005.
  • 45
    Kong YY, Feige U, Sarosi I, Bolon B, Tafuri A, Morony S, et al. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 1999; 402: 3049.
  • 46
    Hashizume M, Hayakawa N, Mihara M. IL-6 trans-signalling directly induces RANKL on fibroblast-like synovial cells and is involved in RANKL induction by TNF-α and IL-17. Rheumatology (Oxford) 2008; 47: 163540.