Table of Contents Author Guidelines Submit a Manuscript
Analytical Cellular Pathology
Volume 2015 (2015), Article ID 434389, 10 pages
http://dx.doi.org/10.1155/2015/434389
Review Article

The Role of “Bone Immunological Niche” for a New Pathogenetic Paradigm of Osteoporosis

1Institute of Internal Medicine, Catholic University of the Sacred Heart, Largo A. Gemelli 8, 00168 Rome, Italy
2Institute of Orthopedics, Catholic University of the Sacred Heart, Largo A. Gemelli 8, 00168 Rome, Italy
3CytoCure LLC, 100 Cummings Center, Suite 430C, Beverly, MA 01915, USA

Received 1 April 2015; Accepted 9 September 2015

Academic Editor: Maryou Lambros

Copyright © 2015 Danilo Pagliari et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. E. Canalis, “Update in new anabolic therapies for osteoporosis,” Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 4, pp. 1496–1504, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. F. Yuan, X. Li, W. Lu et al., “Type 17 T-helper cells might be a promising therapeutic target for osteoporosis,” Molecular Biology Reports, vol. 39, no. 1, pp. 771–774, 2012. View at Publisher · View at Google Scholar
  3. M.-A. El Azreq, M. Boisvert, A. Cesaro et al., “α2β1 integrin regulates Th17 cell activity and its neutralization decreases the severity of collagen-induced arthritis,” Journal of Immunology, vol. 191, no. 12, pp. 5941–5950, 2013. View at Publisher · View at Google Scholar · View at Scopus
  4. N. A. Sims and N. C. Walsh, “Intercellular cross-talk among bone cells: new factors and pathways,” Current Osteoporosis Reports, vol. 10, no. 2, pp. 109–117, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. U. Syrbe and B. Siegmund, “Bone marrow Th17 TNFalpha cells induce osteoclast differentiation and link bone destruction to IBD,” Gut, vol. 64, no. 7, pp. 1011–1012, 2015. View at Publisher · View at Google Scholar
  6. R. R. McLean, “Proinflammatory cytokines and osteoporosis,” Current Osteoporosis Reports, vol. 7, no. 4, pp. 134–139, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. S. H. Tella and J. C. Gallagher, “Prevention and treatment of postmenopausal osteoporosis,” Journal of Steroid Biochemistry and Molecular Biology, vol. 142, pp. 155–170, 2014. View at Publisher · View at Google Scholar · View at Scopus
  8. B. K. Park, H. Zhang, Q. Zeng et al., “NF-κB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF,” Nature Medicine, vol. 13, no. 1, pp. 62–69, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. M. Esposito and Y. Kang, “Targeting tumor-stromal interactions in bone metastasis,” Pharmacology and Therapeutics, vol. 141, no. 2, pp. 222–223, 2014. View at Publisher · View at Google Scholar · View at Scopus
  10. D. L. Lacey, W. J. Boyle, W. S. Simonet et al., “Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab,” Nature Reviews Drug Discovery, vol. 11, no. 5, pp. 401–419, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. D. Vega, N. M. Maalouf, and K. Sakhaee, “CLINICAL review #: the role of receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/osteoprotegerin: clinical implications,” The Journal of Clinical Endocrinology & Metabolism, vol. 92, no. 12, pp. 4514–4521, 2007. View at Google Scholar
  12. W. S. Simonet, D. L. Lacey, C. R. Dunstan et al., “Osteoprotegerin: a novel secreted protein involved in the regulation of bone density,” Cell, vol. 89, no. 2, pp. 309–319, 1997. View at Publisher · View at Google Scholar · View at Scopus
  13. P. Geusens, “Emerging treatments for postmenopausal osteoporosis—focus on denosumab,” Clinical Interventions in Aging, vol. 4, pp. 241–250, 2009. View at Google Scholar · View at Scopus
  14. L. D'Amico and I. Roato, “Cross-talk between T cells and osteoclasts in bone resorption,” BoneKEy Reports, vol. 1, no. 6, article 82, 2012. View at Publisher · View at Google Scholar
  15. T. Kawai, T. Matsuyama, Y. Hosokawa et al., “B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease,” The American Journal of Pathology, vol. 169, no. 3, pp. 987–998, 2006. View at Publisher · View at Google Scholar · View at Scopus
  16. A. E. Kearns, S. Khosla, and P. J. Kostenuik, “Receptor activator of nuclear factor κB ligand and osteoprotegerin regulation of bone remodeling in health and disease,” Endocrine Reviews, vol. 29, no. 2, pp. 155–192, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. T. J. De Vries, T. Schoenmaker, D. Aerts et al., “M-CSF priming of osteoclast precursors can cause osteoclastogenesis-insensitivity, which can be prevented and overcome on bone,” Journal of Cellular Physiology, vol. 230, no. 1, pp. 210–225, 2015. View at Publisher · View at Google Scholar · View at Scopus
  18. B. F. Boyce and L. Xing, “Biology of RANK, RANKL, and osteoprotegerin,” Arthritis Research & Therapy, vol. 9, no. 1, article S1, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. L. C. Hofbauer and M. Schoppet, “Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases,” Journal of the American Medical Association, vol. 292, no. 4, pp. 490–495, 2004. View at Publisher · View at Google Scholar · View at Scopus
  20. Y. Gao, F. Grassi, M. R. Ryan et al., “IFN-γ stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation,” Journal of Clinical Investigation, vol. 117, no. 1, pp. 122–132, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. R. Senthilkumar and H.-W. Lee, “CD137L- and RANKL-mediated reverse signals inhibit osteoclastogenesis and T lymphocyte proliferation,” Immunobiology, vol. 214, no. 2, pp. 153–161, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. P. DAmelio, I. Roato, L. Damico et al., “Bone and bone marrow pro-osteoclastogenic cytokines are up-regulated in osteoporosis fragility fractures,” Osteoporosis International, vol. 22, no. 11, pp. 2869–2877, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. F. Pandolfi, R. Cianci, D. Pagliari, R. Landolfi, S. Kunkel, and G. Cammarota, “Cellular mediators of inflammation: tregs and T H 17 cells in gastrointestinal diseases,” Mediators of Inflammation, vol. 2009, Article ID 132028, 11 pages, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. X. Li, F. L. Yuan, W. G. Lu et al., “The role of interleukin-17 in mediating joint destruction in rheumatoid arthritis,” Biochemical and Biophysical Research Communications, vol. 397, no. 2, pp. 131–135, 2010. View at Google Scholar
  25. C. Dong, “Differentiation and function of pro-inflammatory Th17 cells,” Microbes and Infection, vol. 11, no. 5, pp. 584–588, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. D. Pagliari, R. Cianci, S. Frosali et al., “The role of IL-15 in gastrointestinal diseases: a bridge between innate and adaptive immune response,” Cytokine & Growth Factor Reviews, vol. 24, no. 5, pp. 455–466, 2013. View at Publisher · View at Google Scholar · View at Scopus
  27. R. Cianci, G. Cammarota, G. Frisullo et al., “Tissue-infiltrating lymphocytes analysis reveals large modifications of the duodenal ‘immunological niche’ in coeliac disease after gluten-free diet,” Clinical and Translational Gastroenterology, vol. 3, article e28, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. J.-S. Park, S.-K. Kwok, M.-A. Lim et al., “STA-21, a promising STAT-3 inhibitor that reciprocally regulates Th17 and Treg cells, inhibits osteoclastogenesis in mice and humans and alleviates autoimmune inflammation in an experimental model of rheumatoid arthritis,” Arthritis and Rheumatology, vol. 66, no. 4, pp. 918–929, 2014. View at Publisher · View at Google Scholar · View at Scopus
  29. K. Sato, A. Suematsu, K. Okamoto et al., “Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction,” Journal of Experimental Medicine, vol. 203, no. 12, pp. 2673–2682, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. L. Rifas and M. N. Weitzmann, “A novel T cell cytokine, secreted osteoclastogenic factor of activated T cells, induces osteoclast formation in a RANKL-independent manner,” Arthritis & Rheumatism, vol. 60, no. 11, pp. 3324–3335, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. A. E. Oostlander, V. Everts, T. Schoenmaker et al., “T cell-mediated increased osteoclast formation from peripheral blood as a mechanism for crohn's disease-associated bone loss,” Journal of Cellular Biochemistry, vol. 113, no. 1, pp. 260–268, 2012. View at Publisher · View at Google Scholar · View at Scopus
  32. T. Korn, M. Oukka, V. Kuchroo, and E. Bettelli, “Th17 cells: effector T cells with inflammatory properties,” Seminars in Immunology, vol. 19, no. 6, pp. 362–371, 2007. View at Publisher · View at Google Scholar · View at Scopus
  33. K. Okamoto and H. Takayanagi, “Regulation of bone by the adaptive immune system in arthritis,” Arthritis Research & Therapy, vol. 13, no. 3, article 219, 2011. View at Publisher · View at Google Scholar · View at Scopus
  34. R. Zhao, “Immune regulation of bone loss by Th17 cells in oestrogen-deficient osteoporosis,” European Journal of Clinical Investigation, vol. 43, no. 11, pp. 1195–1202, 2013. View at Publisher · View at Google Scholar · View at Scopus
  35. M. F. Faienza, A. Ventura, F. Marzano, and L. Cavallo, “Postmenopausal osteoporosis: the role of immune system cells,” Clinical and Developmental Immunology, vol. 2013, Article ID 575936, 6 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  36. T. Mori, T. Miyamoto, H. Yoshida et al., “IL-1β and TNFα-initiated IL-6-STAT3 pathway is critical in mediating inflammatory cytokines and RANKL expression in inflammatory arthritis,” International Immunology, vol. 23, no. 11, pp. 701–712, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. T. J. Harris, J. F. Grosso, H.-R. Yen et al., “An in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity,” Journal of Immunology, vol. 179, no. 7, pp. 4313–4317, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. A. S. K. de Hooge, F. A. J. van de Loo, M. I. Koenders et al., “Local activation of STAT-1 and STAT-3 in the inflamed synovium during zymosan-induced arthritis: exacerbation of joint inflammation in STAT-1 gene-knockout mice,” Arthritis and Rheumatism, vol. 50, no. 6, pp. 2014–2023, 2004. View at Publisher · View at Google Scholar · View at Scopus
  39. H. Song, R. Wang, S. Wang, and J. Lin, “A low-molecular-weight compound discovered through virtual database screening inhibits Stat3 function in breast cancer cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 13, pp. 4700–4705, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. H. Saleh, D. Eeles, J. M. Hodge et al., “Interleukin-33, a target of parathyroid hormone and oncostatin m, increases osteoblastic matrix mineral deposition and inhibits osteoclast formation in vitro,” Endocrinology, vol. 152, no. 5, pp. 1911–1922, 2011. View at Publisher · View at Google Scholar · View at Scopus
  41. M. M. Zaiss, R. Axmann, J. Zwerina et al., “Treg cells suppress osteoclast formation: a new link between the immune system and bone,” Arthritis & Rheumatism, vol. 56, no. 12, pp. 4104–4112, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. M. M. Zaiss, B. Frey, A. Hess et al., “Regulatory T cells protect from local and systemic bone destruction in arthritis,” Journal of Immunology, vol. 184, no. 12, pp. 7238–7246, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. M. M. Zaiss, K. Sarter, A. Hess et al., “Increased bone density and resistance to ovariectomy-induced bone loss in FoxP3-transgenic mice based on impaired osteoclast differentiation,” Arthritis and Rheumatism, vol. 62, no. 8, pp. 2328–2338, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. A. R. Pettit, M. K. Chang, D. A. Hume, and L.-J. Raggatt, “Osteal macrophages: a new twist on coupling during bone dynamics,” Bone, vol. 43, no. 6, pp. 976–982, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. M. K. Chang, L.-J. Raggatt, K. A. Alexander et al., “Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo,” Journal of Immunology, vol. 181, no. 2, pp. 1232–1244, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. R. Cianci, D. Pagliari, R. Landolfi et al., “New insights on the role of T cells in the pathogenesis of celiac disease,” Journal of Biological Regulators and Homeostatic Agents, vol. 26, no. 2, pp. 171–179, 2012. View at Google Scholar · View at Scopus
  47. L. Shang, M. Fukata, N. Thirunarayanan et al., “Toll-like receptor signaling in small intestinal epithelium promotes B-cell recruitment and IgA production in lamina propria,” Gastroenterology, vol. 135, no. 2, pp. 529.e1–538.e1, 2008. View at Publisher · View at Google Scholar · View at Scopus
  48. R. Cianci, S. Frosali, D. Pagliari et al., “Uncomplicated diverticular disease: innate and adaptive immunity in human gut mucosa before and after rifaximin,” Journal of Immunology Research, vol. 2014, Article ID 696812, 11 pages, 2014. View at Publisher · View at Google Scholar
  49. T. Krisher and Z. Bar-Shavit, “Regulation of osteoclastogenesis by integrated signals from toll-like receptors,” Journal of Cellular Biochemistry, vol. 115, no. 12, pp. 2146–2154, 2014. View at Publisher · View at Google Scholar
  50. B. Henderson and S. P. Nair, “Hard labour: bacterial infection of the skeleton,” Trends in Microbiology, vol. 11, no. 12, pp. 570–577, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. A. Amcheslavsky and Z. Bar-Shavit, “Toll-like receptor 9 ligand blocks osteoclast differentiation through induction of phosphatase,” Journal of Bone and Mineral Research, vol. 22, no. 8, pp. 1301–1310, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. A. Shekaran, J. T. Shoemaker, T. E. Kavanaugh et al., “The effect of conditional inactivation of beta 1 integrins using twist 2 Cre, Osterix Cre and osteocalcin Cre lines on skeletal phenotype,” Bone, vol. 68, pp. 131–141, 2014. View at Publisher · View at Google Scholar · View at Scopus
  53. Y.-P. Lin, C.-C. Su, J.-Y. Huang et al., “Aberrant integrin activation induces p38 MAPK phosphorylation resulting in suppressed Fas-mediated apoptosis in T cells: implications for rheumatoid arthritis,” Molecular Immunology, vol. 46, no. 16, pp. 3328–3335, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Boisvert, N. Chetoui, S. Gendron, and F. Aoudjit, “Alpha2beta1 integrin is the major collagen-binding integrin expressed on human Th17 cells,” European Journal of Immunology, vol. 40, no. 10, pp. 2710–2719, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. K. Tokoyoda, S. Zehentmeier, A. N. Hegazy et al., “Professional Memory CD4+ T Lymphocytes Preferentially Reside and Rest in the Bone Marrow,” Immunity, vol. 30, no. 5, pp. 721–730, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. S. Brenner, N. Whiting-Theobald, T. Kawai et al., “CXCR4-transgene expression significantly improves marrow engraftment of cultured hematopoietic stem cells,” Stem Cells, vol. 22, no. 7, pp. 1128–1133, 2004. View at Publisher · View at Google Scholar · View at Scopus
  57. C. Hayashi, S. Rittling, T. Hayata et al., “Serum osteopontin, an enhancer of tumor metastasis to bone, promotes B16 melanoma cell migration,” Journal of Cellular Biochemistry, vol. 101, no. 4, pp. 979–986, 2007. View at Publisher · View at Google Scholar · View at Scopus
  58. C. L. Hall, C. W. Dubyk, T. A. Riesenberger, D. Shein, E. T. Keller, and K. L. Van Golen, “Type I collagen receptor (α2β1) signaling promotes prostate cancer invasion through RhoC GTPase,” Neoplasia, vol. 10, no. 8, pp. 797–803, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. Y.-S. Guo, R. Zhao, J. Ma et al., “βig-h3 promotes human osteosarcoma cells metastasis by interacting with integrin α2β1 and activating PI3K signaling pathway,” PLoS ONE, vol. 9, no. 3, Article ID e90220, 2014. View at Publisher · View at Google Scholar · View at Scopus
  60. S. R. Barthel, D. L. Hays, E. M. Yazawa et al., “Definition of molecular determinants of prostate cancer cell bone extravasation,” Cancer Research, vol. 73, no. 2, pp. 942–952, 2013. View at Publisher · View at Google Scholar · View at Scopus
  61. A. Shekaran, J. R. García, A. Y. Clark et al., “Bone regeneration using an alpha 2 beta 1 integrin-specific hydrogel as a BMP-2 delivery vehicle,” Biomaterials, vol. 35, no. 21, pp. 5453–5461, 2014. View at Publisher · View at Google Scholar · View at Scopus
  62. P. Bailon and C.-Y. Won, “PEG-modified biopharmaceuticals,” Expert Opinion on Drug Delivery, vol. 6, no. 1, pp. 1–16, 2009. View at Publisher · View at Google Scholar · View at Scopus
  63. G. R. Mundy, “Metastasis to bone: causes, consequences and therapeutic opportunities,” Nature Reviews Cancer, vol. 2, no. 8, pp. 584–593, 2002. View at Publisher · View at Google Scholar · View at Scopus
  64. M. R. McClung, E. Michael Lewiecki, S. B. Cohen et al., “Denosumab in postmenopausal women with low bone mineral density,” The New England Journal of Medicine, vol. 354, no. 8, pp. 821–831, 2006. View at Publisher · View at Google Scholar · View at Scopus