Best Practice & Research Clinical Rheumatology
Volume 24, Issue 4 , Pages 489-496 , August 2010

Novel targets in bone and cartilage

References1 

  1. Schett G. Joint remodelling in inflammatory disease. Annals of the Rheumatic Diseases. 2007;66(Suppl. 3):iii42–iii44
  2. Redlich K, Hayer S, Ricci R, et al. Osteoclasts are essential for TNF-alpha-mediated joint destruction. The Journal of Clinical Investigation. 2002;110(10):1419–1427
  3. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423(6937):337–342
  4. Goldring MB, Marcu KB. Cartilage homeostasis in health and rheumatic diseases. Arthritis Research & Therapy. 2009;11(3):224
  5. Lam J, Takeshita S, Barker JE, et al. TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. The Journal of Clinical Investigation. 2000;106(12):1481–1488
  6. Lubberts E, van den Bersselaar L, Oppers-Walgreen B, et al. IL-17 promotes bone erosion in murine collagen-induced arthritis through loss of the receptor activator of NF-kappa B ligand/osteoprotegerin balance. Journal of Immunology. 2003;170(5):2655–2662
  7. Sato K, Suematsu A, Okamoto K, et al. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. The Journal of Experimental Medicine. 2006;203(12):2673–2682
  8. Wei S, Kitaura H, Zhou P, et al. IL-1 mediates TNF-induced osteoclastogenesis. The Journal of Clinical Investigation. 2005;115(2):282–290
  9. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nature Reviews. Immunology. 2007;7(6):429–442
  10. Takayanagi H. Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nature Reviews. Immunology. 2007;7(4):292–304
  11. Gravallese EM, Manning C, Tsay A, et al. Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor. Arthritis and Rheumatism. 2000;43(2):250–258
  12. Vasiljeva O, Reinheckel T, Peters C, et al. Emerging roles of cysteine cathepsins in disease and their potential as drug targets. Current Pharmaceutical Design. 2007;13(4):387–403
  13. In:  Smolen JS,  Lipsky PE editor. Biological therapies in rheumatology. London: Taylor & Francis Ltd.; 2002;
  14. Kong YY, Yoshida H, Sarosi I, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999;397(6717):315–323
  15. Lacey DL, Timms E, Tan HL, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93(2):165–176
  16. Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89(2):309–319
  17. Romas E, Sims NA, Hards DK, et al. Osteoprotegerin reduces osteoclast numbers and prevents bone erosion in collagen-induced arthritis. The American Journal of Pathology. 2002;161(4):1419–1427
  18. Redlich K, Gortz B, Hayer S, et al. Repair of local bone erosions and reversal of systemic bone loss upon therapy with anti-tumor necrosis factor in combination with osteoprotegerin or parathyroid hormone in tumor necrosis factor-mediated arthritis. The American Journal of Pathology. 2004;164(2):543–555
  19. Schett G, Middleton S, Bolon B, et al. Additive bone-protective effects of anabolic treatment when used in conjunction with RANKL and tumor necrosis factor inhibition in two rat arthritis models. Arthritis and Rheumatism. 2005;52(5):1604–1611
  20. Kong YY, Feige U, Sarosi I, et al. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature. 1999;402(6759):304–309
  21. Bolon B, Campagnuolo G, Feige U. Duration of bone protection by a single osteoprotegerin injection in rats with adjuvant-induced arthritis. Cellular and Molecular Life Sciences. 2002;59(9):1569–1576
  22. Schett G, Stolina M, Dwyer D, et al. Tumor necrosis factor alpha and RANKL blockade cannot halt bony spur formation in experimental inflammatory arthritis. Arthritis and Rheumatism. 2009;60(9):2644–2654
  23. Flick LM, Weaver JM, Ulrich-Vinther M, et al. Effects of receptor activator of NFkappaB (RANK) signalling blockade on fracture healing. Journal of Orthopaedic Research. 2003;21(4):676–684
  24. Stolina M, Schett G, Dwyer D, et al. RANKL inhibition by osteoprotegerin prevents bone loss without affecting local or systemic inflammation parameters in two rat arthritis models: comparison with anti-TNFalpha or anti-IL-1 therapies. Arthritis Research & Therapy. 2009;11(6):R187
  25. Schett G, Hayer S, Zwerina J, et al. Mechanisms of disease: the link between RANKL and arthritic bone disease. Nature Clinical Practice. Rheumatology. 2005;1(1):47–54
  26. Bekker PJ, Holloway D, Nakanishi A, et al. The effect of a single dose of osteoprotegerin in postmenopausal women. Journal of Bone and Mineral Research. 2001;16(2):348–360
  27. Body JJ, Greipp P, Coleman RE, et al. A phase I study of AMGN-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases. Cancer. 2003;97(3 Suppl.):887–892
  28. Bekker PJ, Holloway DL, Rasmussen AS, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. 2004. Journal of Bone and Mineral Research. 2005;20(12):2275–2282
  29. McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in postmenopausal women with low bone mineral density. The New England Journal of Medicine. 2006;354(8):821–831
  30. Eggelmeijer F, Papapoulos SE, van Paassen HC, et al. Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three-year randomized, double-blind trial. Arthritis and Rheumatism. 1996;39(3):396–402
  31. Maccagno A, Di Giorgio E, Roldan EJ, et al. Double blind radiological assessment of continuous oral pamidronic acid in patients with rheumatoid arthritis. Scandinavian Journal of Rheumatology. 1994;23(4):211–214
  32. Ralston SH, Hacking L, Willocks L, et al. Clinical, biochemical, and radiographic effects of aminohydroxypropylidene bisphosphonate treatment in rheumatoid arthritis. Annals of the Rheumatic Diseases. 1989;48(5):396–399
  33. Cohen SB, Dore RK, Lane NE, et al. Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis and Rheumatism. 2008;58(5):1299–1309
  34. Li X, Liu P, Liu W, et al. Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation. Nature Genetics. 2005;37(9):945–952
  35. Li X, Zhang Y, Kang H, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signalling. The Journal of Biological Chemistry. 2005;280(20):19883–19887
  36. Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling. Nature Medicine. 2007;13(2):156–163
  37. Ettenberg S, Cong F, Shulok J, et al. BHQ880, a novel anti-DKK1 neutralizing antibody, inhibits tumor-induced osteolytic bone disease. American Association for Cancer Research Annual Meeting, April 12–16, 2008, San Diego, California.
  38. Choi HY, Dieckmann M, Herz J, Niemeier A. Lrp4, a novel receptor for Dickkopf 1 and sclerostin, is expressed by osteoblasts and regulates bone growth and turnover in vivo. PLoS One. 2009;4(11):e7930
  39. Winkler DG, Sutherland MS, Ojala E, et al. Sclerostin inhibition of Wnt-3a-induced C3H10T1/2 cell differentiation is indirect and mediated by bone morphogenetic proteins. The Journal of Biological Chemistry. 2005;280(4):2498–2502
  40. Semenov M, Tamai K, He X. SOST is a ligand for LRP5/LRP6 and a Wnt signalling inhibitor. The Journal of Biological Chemistry. 2005;280(29):26770–26775
  41. Loots GG, Kneissel M, Keller H, et al. Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease. Genome Research. 2005;15(7):928–935
  42. Winkler DG, Sutherland MK, Geoghegan JC, et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. The EMBO Journal. 2003;22(23):6267–6276
  43. Li X, Ominsky MS, Niu QT, et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. Journal of Bone and Mineral Research. 2008;23(6):860–869
  44. Brunkow ME, Gardner JC, Van Ness J, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. American Journal of Human Genetics. 2001;68(3):577–589
  45. Appel H, Ruiz-Heiland G, Listing J, et al. Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis and Rheumatism. 2009;60(11):3257–3262
  46. Poole KE, van Bezooijen RL, Loveridge N, et al. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. The FASEB Journal. 2005;19(13):1842–1844
  47. Dong Y, Drissi H, Chen M, et al. Wnt-mediated regulation of chondrocyte maturation: modulation by TGF-beta. Journal of Cellular Biochemistry. 2005;95(5):1057–1068
  48. Chen M, Zhu M, Awad H, et al. Inhibition of beta-catenin signalling causes defects in postnatal cartilage development. Journal of Cell Science. 2008;121(Pt 9):1455–1465
  49. Yuasa T, Otani T, Koike T, et al. Wnt/beta-catenin signalling stimulates matrix catabolic genes and activity in articular chondrocytes: its possible role in joint degeneration. Laboratory Investigation. 2008;88(3):264–274
  50. Lories RJ, Peeters J, Bakker A, et al. Articular cartilage and biomechanical properties of the long bones in Frzb-knockout mice. Arthritis and Rheumatism. 2007;56(12):4095–4103
  51. Chen Y, Whetstone HC, Lin AC, et al. Beta-catenin signalling plays a disparate role in different phases of fracture repair: implications for therapy to improve bone healing. PLoS Med. 2007;4(7):e249
  52. Dell’accio F, De Bari C, Eltawil NM, et al. Identification of the molecular response of articular cartilage to injury, by microarray screening: Wnt-16 expression and signalling after injury and in osteoarthritis. Arthritis and Rheumatism. 2008;58(5):1410–1421
  53. Kakar S, Einhorn TA, Vora S, et al. Enhanced chondrogenesis and Wnt signalling in PTH-treated fractures. Journal of Bone and Mineral Research. 2007;22(12):1903–1912
  54. Stoch SA, Wagner JA. Cathepsin K inhibitors: a novel target for osteoporosis therapy. Clinical Pharmacology and Therapeutics. 2008;83(1):172–176
  55. Schurigt U, Hummel KM, Petrow PK, et al. Cathepsin K deficiency partially inhibits, but does not prevent, bone destruction in human tumor necrosis factor-transgenic mice. Arthritis and Rheumatism. 2008;58(2):422–434
  56. Asagiri M, Hirai T, Kunigami T, et al. Cathepsin K-dependent toll-like receptor 9 signalling revealed in experimental arthritis. Science. 2008;319(5863):624–627
  57. Deal C. Future therapeutic targets in osteoporosis. Current Opinion in Rheumatology. 2009;21(4):380–385
  58. Adami S, Supronik J, Hala T. Effect of one year treatment with the cathepsin-K inhibitor, balicatib, on bone mineral density (BMD) in postmenopausal women with osteopenia/osteoporosis. Journal of Bone and Mineral Research. 2006;21(Suppl. 1):Abstract 1085
  59. Papanastasiou P, Ortmann C, Olson M. Effect of three month treatment with the cathepsin-K inhibitor, balicatib, on biochemical markers of bone turnover in postmenopausal women: evidence for uncoupling of bone resorption and bone formation. Journal of Bone and Mineral Research. 2006;21(Suppl. 1):Abstract 1223
  60. Stoch SA, Zajic S, Stone J, et al. Effect of the cathepsin K inhibitor odanacatib on bone resorption biomarkers in healthy postmenopausal women: two double-blind, randomized, placebo-controlled phase I studies. Clinical Pharmacology and Therapeutics. 2009;86(2):175–182
  61. Deschaseaux F, Sensebe L, Heymann D. Mechanisms of bone repair and regeneration. Trends in Molecular Medicine. 2009;15(9):417–429
  62. Ohba S, Kawaguchi H, Kugimiya F, et al. Patched1 haploinsufficiency increases adult bone mass and modulates Gli3 repressor activity. Developmental Cell. 2008;14(5):689–699
  63. Mak KK, Bi Y, Wan C, et al. Hedgehog signalling in mature osteoblasts regulates bone formation and resorption by controlling PTHrP and RANKL expression. Developmental Cell. 2008;14(5):674–688
  64. Lin AC, Seeto BL, Bartoszko JM, et al. Modulating hedgehog signalling can attenuate the severity of osteoarthritis. Nature Medicine. 2009;15(12):1421–1425
  65. Lum L, Beachy PA. The Hedgehog response network: sensors, switches, and routers. Science. 2004;304(5678):1755–1759
  66. Ng TC, Chiu KW, Rabie AB, Hagg U. Repeated mechanical loading enhances the expression of Indian hedgehog in condylar cartilage. Frontiers in Bioscience. 2006;11:943–948
  67. Aigner T, Soder S, Gebhard PM, et al. Mechanisms of disease: role of chondrocytes in the pathogenesis of osteoarthritis–structure, chaos and senescence. Nature Clinical Practice. Rheumatology. 2007;3(7):391–399
  68. Ornitz DM. FGFs, heparan sulfate and FGFRs: complex interactions essential for development. Bioessays. 2000;22(2):108–112
  69. Liu Z, Xu J, Colvin JS, Ornitz DM. Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18. Genes & Development. 2002;16(7):859–869
  70. Eswarakumar VP, Monsonego-Ornan E, Pines M, et al. The IIIc alternative of Fgfr2 is a positive regulator of bone formation. Development. 2002;129(16):3783–3793
  71. Ornitz DM, Marie PJ. FGF signalling pathways in endochondral and intramembranous bone development and human genetic disease. Genes & Development. 2002;16(12):1446–1465
  72. Ellsworth JL, Berry J, Bukowski T, et al. Fibroblast growth factor-18 is a trophic factor for mature chondrocytes and their progenitors. Osteoarthritis Cartilage. 2002;10(4):308–320
  73. Davidson D, Blanc A, Filion D, et al. Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis. The Journal of Biological Chemistry. 2005;280(21):20509–20515
  74. Ohbayashi N, Shibayama M, Kurotaki Y, et al. FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. Genes & Development. 2002;16(7):870–879
  75. Yamaoka H, Nishizawa S, Asawa Y, et al. Involvement of fibroblast growth factor 18 in dedifferentiation of cultured human chondrocytes. Cell Proliferation. 2010;43(1):67–76
  76. Moore EE, Bendele AM, Thompson DL, et al. Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. Osteoarthritis Cartilage. 2005;13(7):623–631

PII: S1521-6942(10)00028-8

doi: 10.1016/j.berh.2010.03.001

Best Practice & Research Clinical Rheumatology
Volume 24, Issue 4 , Pages 489-496 , August 2010

Article Tools

* Image Usage & Resolution