Osteoclasts: Crucial in Rheumatoid Arthritis

Won-Ju Jeong; Ha-Jeong Kim

doi:10.4078/jrd.2016.23.3.141

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Jeong and Kim: Osteoclasts: Crucial in Rheumatoid Arthritis

Review Article

J Rheum Dis 2016;23(3):141-147.

Published online: 31 October 2016

DOI: https://doi.org/10.4078/jrd.2016.23.3.141

Osteoclasts: Crucial in Rheumatoid Arthritis

Won-Ju Jeong¹, Ha-Jeong Kim²

¹Department of Orthopedic Surgery, Kyungpook National University School of Medicine, Daegu, Korea

²Department of Physiology, Kyungpook National University School of Medicine, Daegu, Korea

Corresponding to: Ha-Jeong Kim, Department of Physiology, Kyungpook National University School of Medicine, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Korea. E-mail: kimhajeong@knu.ac.kr

Received 9 May 201614 June 2016 Accepted 14 June 2016

This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Osteoclasts are a major component of bone metabolism in physiologic condition and in rheumatoid arthritis (RA). RA is a chronic, autoimmune, inflammatory disease primarily affecting the joints. Joint inflammation leads to cartilage and bone destruction by osteoclast activation. This osteoclast activation leads to typical RA symptoms and is the therapeutic target. Several kinds of drugs are used for preventing bone loss by osteoclasts in RA patients. However, the bone destructive action of osteoclasts is not the only mechanism in RA pathogenesis. Recent research suggests that the osteoclasts regulate hematopoietic stem cell niches and invoke immune responses in bone. Osteoclasts are derived from bone marrow hematopoietic stem cells, and maintain the hematopoietic stem cell niches contract with osteoblasts. Osteoclasts secret several cytokines to regulate inflammation and T cell differentiation, and present antigen to T cells via major histocompatibility complex class I and class II molecules. Osteoclast concepts in both origins and functions are under major reconsideration and research. In this review, we will discuss these new insights.

Keywords: Osteoclasts, Osteoclastogenesis, Rheumatoid arthritis, RANK ligand, Immunity

REFERENCES

1. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003; 423:337–42.

2. Firestein GS. Evolving concepts of rheumatoid arthritis. Nature. 2003; 423:356–61.

3. Shaw AT, Gravallese EM. Mediators of inflammation and bone remodeling in rheumatic disease. Semin Cell Dev Biol. 2016; 49:2–10.

4. Brzustewicz E, Bryl E. The role of cytokines in the pathogenesis of rheumatoid arthritis− Practical and potential application of cytokines as biomarkers and targets of personalized therapy. Cytokine. 2015; 76:527–36.

5. Karsdal MA, Martin TJ, Bollerslev J, Christiansen C, Henriksen K. Are nonresorbing osteoclasts sources of bone anabolic activity? J Bone Miner Res. 2007; 22:487–94.

6. Mansour A, Abou-Ezzi G, Sitnicka E, Jacobsen SE, Wakkach A, Blin-Wakkach C. Osteoclasts promote the formation of hematopoietic stem cell niches in the bone marrow. J Exp Med. 2012; 209:537–49.

7. Mansour A, Wakkach A, Blin-Wakkach C. Role of osteoclasts in the hematopoietic stem cell niche formation. Cell Cycle. 2012; 11:2045–6.

8. Yao Z, Xing L, Qin C, Schwarz EM, Boyce BF. Osteoclast precursor interaction with bone matrix induces osteoclast formation directly by an interleukin-1-mediated autocrine mechanism. J Biol Chem. 2008; 283:9917–24.

9. Charles JF, Aliprantis AO. Osteoclasts: more than ‘bone eaters’. Trends Mol Med. 2014; 20:449–59.

10. Takahashi N, Yamana H, Yoshiki S, Roodman GD, Mundy GR, Jones SJ, et al. Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinology. 1988; 122:1373–82.

11. Pettit AR, Ji H, von Stechow D, Müller R, Goldring SR, Choi Y, et al. TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. Am J Pathol. 2001; 159:1689–99.

12. Takayanagi H. Osteoimmunology and the effects of the immune system on bone. Nat Rev Rheumatol. 2009; 5:667–76.

13. 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; 402:304–9.

14. Horwood NJ, Kartsogiannis V, Quinn JM, Romas E, Martin TJ, Gillespie MT. Activated T lymphocytes support osteoclast formation in vitro. Biochem Biophys Res Commun. 1999; 265:144–50.

15. Kotake S, Udagawa N, Hakoda M, Mogi M, Yano K, Tsuda E, et al. 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; 44:1003–12.

16. 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-depend-ent and -independent mechanisms. J Bone Miner Res. 2001; 16:328–37.

17. Wang R, Zhang L, Zhang X, Moreno J, Celluzzi C, Tondravi M, et al. Regulation of activation-induced receptor activator of NF-kappaB ligand (RANKL) expression in T cells. Eur J Immunol. 2002; 32:1090–8.

18. Li P, Schwarz EM, O'Keefe RJ, Ma L, Boyce BF, Xing L. RANK signaling is not required for TNFalpha-mediated increase in CD11(hi) osteoclast precursors but is essential for mature osteoclast formation in TNFalpha-mediated inflammatory arthritis. J Bone Miner Res. 2004; 19:207–13.

19. Herman S, Müller RB, Krönke G, Zwerina J, Redlich K, Hueber AJ, et al. Induction of osteoclast-associated receptor, a key osteoclast costimulation molecule, in rheumatoid arthritis. Arthritis Rheum. 2008; 58:3041–50.

20. Vervoordeldonk MJ, Tak PP. Cytokines in rheumatoid arthritis. Curr Rheumatol Rep. 2002; 4:208–17.

21. Chizzolini C, Dayer JM, Miossec P. Cytokines in chronic rheumatic diseases: is everything lack of homeostatic bal-ance? Arthritis Res Ther. 2009; 11:246.

22. Takayanagi H, Ogasawara K, Hida S, Chiba T, Murata S, Sato K, et al. T-cell-mediated regulation of osteoclastogenesis by signalling crosstalk between RANKL and IFN-gamma. Nature. 2000; 408:600–5.

23. Ries WL, Seeds MC, Key LL. Interleukin-2 stimulates osteoclastic activity: increased acid production and radioactive calcium release. J Periodontal Res. 1989; 24:242–6.

24. Ashcroft AJ, Cruickshank SM, Croucher PI, Perry MJ, Rollinson S, Lippitt JM, et al. Colonic dendritic cells, intestinal inflammation, and T cell-mediated bone destruction are modulated by recombinant osteoprotegerin. Immunity. 2003; 19:849–61.

25. Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, et al. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med. 2006; 203:2673–82.

26. Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999; 103:1345–52.

27. Sezer O. Myeloma bone disease. Hematology. 2005; 10(Suppl 1):19–24.

28. Raggatt LJ, Partridge NC. Cellular and molecular mechanisms of bone remodeling. J Biol Chem. 2010; 285:25103–8.

29. Li Y, Toraldo G, Li A, Yang X, Zhang H, Qian WP, et al. B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo. Blood. 2007; 109:3839–48.

30. Durand M, Boire G, Komarova SV, Dixon SJ, Sims SM, Harrison RE, et al. The increased in vitro osteoclastogenesis in patients with rheumatoid arthritis is due to increased percentage of precursors and decreased apoptosis – the In Vitro Osteoclast Differentiation in Arthritis (IODA) study. Bone. 2011; 48:588–96.

31. Hirayama T, Danks L, Sabokbar A, Athanasou NA. Osteoclast formation and activity in the pathogenesis of osteoporosis in rheumatoid arthritis. Rheumatology (Oxford). 2002; 41:1232–9.

32. Gravallese EM, Harada Y, Wang JT, Gorn AH, Thornhill TS, Goldring SR. Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis. Am J Pathol. 1998; 152:943–51.

33. Fujikawa Y, Sabokbar A, Neale S, Athanasou NA. Human osteoclast formation and bone resorption by monocytes and synovial macrophages in rheumatoid arthritis. Ann Rheum Dis. 1996; 55:816–22.

34. Rivollier A, Mazzorana M, Tebib J, Piperno M, Aitsiselmi T, Rabourdin-Combe C, et al. Immature dendritic cell trans-differentiation into osteoclasts: a novel pathway sustained by the rheumatoid arthritis microenvironment. Blood. 2004; 104:4029–37.

35. Jacome-Galarza C, Soung do Y, Adapala NS, Pickarski M, Sanjay A, Duong LT, et al. Altered hematopoietic stem cell and osteoclast precursor frequency in cathepsin K null mice. J Cell Biochem. 2014; 115:1449–57.

36. Wakkach A, Mansour A, Dacquin R, Coste E, Jurdic P, Carle GF, et al. Bone marrow microenvironment controls the in vivo differentiation of murine dendritic cells into osteoclasts. Blood. 2008; 112:5074–83.

37. Le Goff B, Berthelot JM, Maugars Y, Heymann D. Osteoclasts in RA: diverse origins and functions. Joint Bone Spine. 2013; 80:586–91.

38. Abou-Ezzi G, Ciucci T, Amiot V, Wakkach A, Blin-Wakkach C. Osteoclasts induce a vicious circle between inflammation and bone destruction. Bone. 2011; 48(Suppl 2):S128.

39. Perez-Amodio S, Jansen DC, Schoenmaker T, Vogels IM, Reinheckel T, Hayman AR, et al. Calvarial osteoclasts express a higher level of tartrate-resistant acid phosphatase than long bone osteoclasts and activation does not depend on cathepsin K or L activity. Calcif Tissue Int. 2006; 79:245–54.

40. Shorey S, Heersche JN, Manolson MF. The relative contribution of cysteine proteinases and matrix metalloproteinases to the resorption process in osteoclasts derived from long bone and scapula. Bone. 2004; 35:909–17.

41. Chappard D, Petitjean M, Alexandre C, Vico L, Minaire P, Riffat G. Cortical osteoclasts are less sensitive to etidronate than trabecular osteoclasts. J Bone Miner Res. 1991; 6:673–80.

42. Bugatti S, Caporali R, Manzo A, Vitolo B, Pitzalis C, Montecucco C. Involvement of subchondral bone marrow in rheumatoid arthritis: lymphoid neogenesis and in situ relationship to subchondral bone marrow osteoclast recruitment. Arthritis Rheum. 2005; 52:3448–59.

43. Hardy R, Cooper MS. Bone loss in inflammatory disorders. J Endocrinol. 2009; 201:309–20.

44. Bar-Shavit Z. Taking a toll on the bones: regulation of bone metabolism by innate immune regulators. Autoimmunity. 2008; 41:195–203.

45. Ji JD, Park-Min KH, Shen Z, Fajardo RJ, Goldring SR, McHugh KP, et al. Inhibition of RANK expression and osteoclastogenesis by TLRs and IFN-gamma in human osteoclast precursors. J Immunol. 2009; 183:7223–33.

46. van Lent PL, Grevers L, Lubberts E, de Vries TJ, Nabbe KC, Verbeek S, et al. Fcgamma receptors directly mediate cartilage, but not bone, destruction in murine antigen-induced arthritis: uncoupling of cartilage damage from bone erosion and joint inflammation. Arthritis Rheum. 2006; 54:3868–77.

47. Grevers LC, de Vries TJ, Everts V, Verbeek JS, van den Berg WB, van Lent PL. Immune complex-induced inhibition of osteoclastogenesis is mediated via activating but not inhibitory Fcγ receptors on myeloid precursor cells. Ann Rheum Dis. 2013; 72:278–85.

48. MacLellan LM, Montgomery J, Sugiyama F, Kitson SM, Thümmler K, Silverman GJ, et al. Co-opting endogenous immunoglobulin for the regulation of inflammation and osteoclastogenesis in humans and mice. Arthritis Rheum. 2011; 63:3897–907.

49. Laurent L, Clavel C, Lemaire O, Anquetil F, Cornillet M, Zabraniecki L, et al. Fcγ receptor profile of monocytes and macrophages from rheumatoid arthritis patients and their response to immune complexes formed with autoantibodies to citrullinated proteins. Ann Rheum Dis. 2011; 70:1052–9.

50. Krishnamurthy A, Joshua V, Haj Hensvold A, Jin T, Sun M, Vivar N, et al. Identification of a novel chemokine-depend-ent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann Rheum Dis. 2016; 75:721–9.

51. Wigerblad G, Bas DB, Fernades-Cerqueira C, Krishnamurthy A, Nandakumar KS, Rogoz K, et al. Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism. Ann Rheum Dis. 2016; 75:730–8.

52. Li H, Hong S, Qian J, Zheng Y, Yang J, Yi Q. Cross talk between the bone and immune systems: osteoclasts function as antigen-presenting cells and activate CD4＋ and CD8＋ T cells. Blood. 2010; 116:210–7.

53. Grassi F, Manferdini C, Cattini L, Piacentini A, Gabusi E, Facchini A, et al. T cell suppression by osteoclasts in vitro. J Cell Physiol. 2011; 226:982–90.

54. Kiesel JR, Buchwald ZS, Aurora R. Cross-presentation by osteoclasts induces FoxP3 in CD8＋ T cells. J Immunol. 2009; 182:5477–87.

55. Kiesel J, Miller C, Abu-Amer Y, Aurora R. Systems level analysis of osteoclastogenesis reveals intrinsic and extrinsic regulatory interactions. Dev Dyn. 2007; 236:2181–97.

56. Harre U, Keppeler H, Ipseiz N, Derer A, Poller K, Aigner M, et al. Moonlighting osteoclasts as undertakers of apoptotic cells. Autoimmunity. 2012; 45:612–9.

57. Pöllinger B, Junt T, Metzler B, Walker UA, Tyndall A, Allard C, et al. Th17 cells, not IL-17＋ γδ T cells, drive arthritic bone destruction in mice and humans. J Immunol. 2011; 186:2602–12.

58. Jacquin C, Gran DE, Lee SK, Lorenzo JA, Aguila HL. Identification of multiple osteoclast precursor populations in murine bone marrow. J Bone Miner Res. 2006; 21:67–77.

59. Charles JF, Hsu LY, Niemi EC, Weiss A, Aliprantis AO, Nakamura MC. Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function. J Clin Invest. 2012; 122:4592–605.

60. Riether C, Schürch CM, Ochsenbein AF. Regulation of hematopoietic and leukemic stem cells by the immune system. Cell Death Differ. 2015; 22:187–98.

61. Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature. 2014; 505:327–34.

62. Kobayashi K, Takahashi N, Jimi E, Udagawa N, Takami M, Kotake S, et al. Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med. 2000; 191:275–86.

63. Kitaura H, Kimura K, Ishida M, Kohara H, Yoshimatsu M, Takano-Yamamoto T. Immunological reaction in TNF-α-mediated osteoclast formation and bone resorption in vitro and in vivo. Clin Dev Immunol. 2013; 2013; 181849.

64. Monaco C, Nanchahal J, Taylor P, Feldmann M. Anti-TNF therapy: past, present and future. Int Immunol. 2015; 27:55–62.

65. Axmann R, Böhm C, Krönke G, Zwerina J, Smolen J, Schett G. Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo. Arthritis Rheum. 2009; 60:2747–56.

66. Boe A, Baiocchi M, Carbonatto M, Papoian R, Serlupi-Crescenzi O. Interleukin 6 knockout mice are resistant to antigen-induced experimental arthritis. Cytokine. 1999; 11:1057–64.

67. Vivar N, Van Vollenhoven RF. Advances in the treatment of rheumatoid arthritis. F1000Prime Rep. 2014; 6:31.

68. Kim JH, Jin HM, Kim K, Song I, Youn BU, Matsuo K, et al. The mechanism of osteoclast differentiation induced by IL-1. J Immunol. 2009; 183:1862–70.

69. Nakamura I, Jimi E. Regulation of osteoclast differentiation and function by interleukin-1. Vitam Horm. 2006; 74:357–70.

70. Jimi E, Nakamura I, Duong LT, Ikebe T, Takahashi N, Rodan GA, et al. Interleukin 1 induces multinucleation and bone-resorbing activity of osteoclasts in the absence of os-teoblasts/stromal cells. Exp Cell Res. 1999; 247:84–93.

71. Lee YM, Fujikado N, Manaka H, Yasuda H, Iwakura Y. IL-1 plays an important role in the bone metabolism under physiological conditions. Int Immunol. 2010; 22:805–16.

72. Singh JA, Christensen R, Wells GA, Suarez-Almazor ME, Buchbinder R, Lopez-Olivo MA, et al. A network metaanalysis of randomized controlled trials of biologics for rheumatoid arthritis: a cochrane overview. CMAJ. 2009; 181:787–96.

73. Venkatesha SH, Dudics S, Acharya B, Moudgil KD. Cytokine-modulating strategies and newer cytokine targets for arthritis therapy. Int J Mol Sci. 2014; 16:887–906.

74. Cohen SB, Dore RK, Lane NE, Ory PA, Peterfy CG, Sharp JT, et al. Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, doubleblind, placebo-controlled, phase II clinical trial. Arthritis Rheum. 2008; 58:1299–309.

Figure 1.

Cross talk between the immune system and osteoclasts in osteoclastogenesis. Osteoclasts are derived from monocyte precursor cells. RANKL from B cell and IL-17 from Th17 cell induces osteoclastogenesis. IL-10 from Treg, IFN-γ from Th1, and IL-4 from Th2 inhibits osteoclastogenesis. I: major histocompatibility complex (MHC) class I, II: MHC class II, IFN: interferon, IL: interleukin, OPG: osteoprotegerin, RANKL: receptor activator of nuclear factor-kappa B ligand, Th1/2/17: T helper cells type 1/2/17, TGF: transforming growth factor, TNF: tumor necrosis factor, Treg: regulatory T cell.

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