1. Okamoto, K. et al. Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems. Physiol. Rev. 97, 1295–1349 (2017).
2. Teti, A. & Zallone, A. Do osteocytes contribute to bone mineral homeostasis? Osteocytic osteolysis revisited. Bone 44, 11–16 (2008).
3. Horton, J. E., Raisz, L. G., Simmons, H. A., Oppenheim, J. J. & Mergenhagen, S. E. Bone resorbing activity in supernatants fluid from cultured human peripheral blood leukocytes. Science (80-. ). 177, 793–795 (1972).
4. Mundy, G. R., Raisz, L. G., Cooper, R. A., Schechter, G. P. & Salmon, S. E. Evidence for the Secretion of an Osteoclast Stimulating Factor in Myeloma. N. Engl. J. Med. 291, 1041–1046 (1974).
5. Feldmann, M., Brennan, F. M. & Maini, R. N. Role of Cytokines in Rheumatoid Arthritis. Annual Review of Immunology 14, (1996).
6. Takayanagi, H. et al. T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-γ. Nature 408, 600–605 (2000).
7. Takahashi, N. et al. Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinology 122, 1373–1382 (1988).
8. Tsuda, E. et al. Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis. Biochemical and Biophysical Research Communications 234, (1997).
9. Simonet, W. S. et al. Osteoprotegerin: A novel secreted protein involved in the regulation of bone density. Cell 89, (1997).
10. Yasuda, H. et al. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): A mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139, (1998).
11. Yasuda, H. 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. 95, 3597–602 (1998).
12. Wong, B. R. et al. TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells. J.Biol.Chem. 272, (1997).
13. Anderson, D. M. et al. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 390, 175–179 (1997).
14. Lacey, D. L. et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93, 165–76 (1998).
15. Kong, Y. Y. et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397, 315–323 (1999).
16. Bucay, N. et al. osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. 12, 1260–8 (1998).
17. Elahi, E. et al. Intragenic SNP haplotypes associated with 84dup18 mutation in TNFRSF11A in four FEO pedigrees suggest three independent origins for this mutation. J. Bone Miner. Metab. 25, 159–164 (2007).
18. Fata, J. E. et al. The Osteoclast Differentiation Factor Osteoprotegerin-Ligand Is Essential for Mammary Gland Development. Cell 103, 41–50 (2000).
19. Anderson, M. S. et al. Projection of an immunological self shadow within the thymus by the aire protein. Science (80-. ). 298, 1395–1401 (2002).
20. Takaba, H. et al. Fezf2 Orchestrates a Thymic Program of Self-Antigen Expression for Immune Tolerance. Cell 163, 975–987 (2015).
21. Hikosaka, Y. et al. The Cytokine RANKL Produced by Positively Selected Thymocytes Fosters Medullary Thymic Epithelial Cells that Express Autoimmune Regulator. Immunity 29, 438–450 (2008).
22. Irla, M. et al. Autoantigen-Specific Interactions with CD4+ Thymocytes Control Mature Medullary Thymic Epithelial Cell Cellularity. Immunity 29, 451–463 (2008).
23. White, A. J. et al. Sequential phases in the development of Aire-expressing medullary thymic epithelial cells involve distinct cellular input. Eur. J. Immunol. 38, 942–947 (2008).
24. Roberts, N. A. et al. Rank Signaling Links the Development of Invariant γδ T Cell Progenitors and Aire + Medullary Epithelium. Immunity 36, 427–437 (2012).
25. White, A. J. et al. An Essential Role for Medullary Thymic Epithelial Cells during the Intrathymic Development of Invariant NKT Cells. J. Immunol. 192, 2659–2666 (2014).
26. Yoshida, H. et al. Different cytokines induce surface lymphotoxin-αβ on IL-7 receptor-α cells that differentially engender lymph nodes and Peyer’s patches. Immunity 17, 823–833 (2002).
27. Akiyama, T. RANKL-RANK interaction in immune regulatory systems. World J. Orthop. 3, 142 (2012).
28. Kim, D. et al. Regulation of peripheral lymph node genesis by the tumor necrosis factor family member TRANCE. J Exp Med 192, 1467–1478 (2000).
29. Onder, L. et al. Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis. Immunity 47, 80–92.e4 (2017).
30. Perlot, T. & Penninger, J. M. Development and Function of Murine B Cells Lacking RANK. J. Immunol. 188, 1201–1205 (2012).
31. Onal, M. et al. Receptor activator of nuclear factor κB ligand (RANKL) protein expression by B lymphocytes contributes to ovariectomy-induced bone loss. J. Biol. Chem. 287, 29851–29860 (2012).
32. Knoop, K. A. et al. RANKL Is Necessary and Sufficient to Initiate Development of Antigen-Sampling M Cells in the Intestinal Epithelium. J. Immunol. 183, 5738–5747 (2009).
33. Nagashima, K. et al. Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota. Nat. Immunol. 18, 675–682 (2017).
34. Fata, J. E. et al. The Osteoclast Differentiation Factor Osteoprotegerin-Ligand Is Essential for Mammary Gland Development dinated resorption by osteoclasts. The TNF family mole-cule Osteoprotegerin-ligand (OPGL; also known as ODF, TRANCE, and RANKL) (Anderson et al is a key factor stimulating the differentiation and activation. Cell 103, (2000).
35. Fernandez-Valdivia, R. & Lydon, J. P. From the ranks of mammary progesterone mediators, RANKL takes the spotlight. (2011). doi:10.1016/j.mce.2011.09.030
36. Schramek, D., Sigl, V. & Penninger, J. M. RANKL and RANK in sex hormone-induced breast cancer and breast cancer metastasis. Trends Endocrinol. Metab. 22, 188–194 (2011).
37. Nakamura, T. et al. Estrogen Prevents Bone Loss via Estrogen Receptor α and Induction of Fas Ligand in Osteoclasts. Cell 130, 811–823 (2007).
38. Martin-Millan, M. et al. The Estrogen Receptor-α in Osteoclasts Mediates the Protective Effects of Estrogens on Cancellous But Not Cortical Bone. Mol. Endocrinol. 24, 323–334 (2010).
39. Määttä, J. A. et al. Inactivation of estrogen receptor in bone-forming cells induces bone loss in female mice. FASEB J. 27, 478–488 (2013).
40. Melville, K. M. et al. Female mice lacking estrogen receptor-alpha in osteoblasts have compromised bone mass and strength. J. Bone Miner. Res. 29, 370–379 (2014).
41. Seitz, S. et al. Pharmacological Estrogen Administration Causes a FSH-Independent Osteo-Anabolic Effect Requiring ER Alpha in Osteoblasts. PLoS One 7, 50301 (2012).
42. Windahl, S. H. et al. Estrogen receptor- in osteocytes is important for trabecular bone formation in male mice. Proc. Natl. Acad. Sci. 110, 2294–2299 (2013).
43. Kondoh, S. et al. Estrogen receptor α in osteocytes regulates trabecular bone formation in female mice. Bone 60, 68–77 (2014).
44. D’Amelio, P. et al. Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: A key mechanism in osteoporosis. Bone 43, 92–100 (2008).
45. Kanematsu, M. et al. Prostaglandin E2induces expression of receptor activator of nuclear factor-κB ligand/osteoprotegrin ligand on pre-B cells: Implications for accelerated osteoclastogenesis in estrogen deficiency. J. Bone Miner. Res. 15, 1321–1329 (2000).
46. Macedo, F. et al. Bone metastases: An overview. Oncol. Rev. 11, (2017).
47. Mundy, G. R. Metastasis to bone: Causes, consequences and therapeutic opportunities. Nat. Rev. Cancer 2, 584–593 (2002).
48. Jones, D. H. et al. Regulation of cancer cell migration and bone metastasis by RANKL. Nature 440, 692–696 (2006).
49. Zhang, L. et al. C-Src-mediated RANKL-induced breast cancer cell migration by activation of the ERK and Akt pathway. Oncol. Lett. 3, 395–400 (2012).
50. Tang, Z. N., Zhang, F., Tang, P., Qi, X. W. & Jiang, J. RANKL-induced migration of MDA-MB-231 human breast cancer cells via Src and MAPK activation. Oncol. Rep. 26, 1243– 1250 (2011).
51. Sakuma, T. et al. CIZ/NMP4 is expressed in B16 melanoma and forms a positive feedback loop with RANKL to promote migration of the melanoma cells. J. Cell. Physiol. 227, 2807–2812 (2012).
52. Weigelt, B., Peterse, J. L. & Van’t Veer, L. J. Breast cancer metastasis: Markers and models. Nat. Rev. Cancer 5, 591–602 (2005).
53. Tan, W. et al. Tumour-infiltrating regulatory T cells stimulate mammary cancermetastasis through RANKL-RANK signalling. Nature 470, 548–553 (2011).
54. Lum, L. et al. Evidence for a role of a tumor necrosis factor-α (TNF-α)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival. J. Biol. Chem. 274, 13613–13618 (1999).
55. Nakashima, T. et al. Protein Expression and Functional Difference of Membrane-Bound and Soluble Receptor Activator of NF-κB Ligand: Modulation of the Expression by Osteotropic Factors and Cytokines. Biochem. Biophys. Res. Commun. 275, 768–775 (2000).
56. Hikita, A. et al. Negative regulation of osteoclastogenesis by ectodomain shedding of receptor activator of NF-κB ligand. J. Biol. Chem. 281, 36846–36855 (2006).
57. Lacey, D. L., Timms, E. & a;, E. Osteoprotegrin ligand is cytokine that regulates osteoclast differentiation and activation. Cell 93, 165–176 (1998).
58. Nelson, C. A., Warren, J. T., Wang, M. W. H., Teitelbaum, S. L. & Fremont, D. H. RANKL employs distinct binding modes to engage RANK and the osteoprotegerin decoy receptor. Structure 20, 1971–1982 (2012).
59. Takahashi, N. et al. Osteoblastic cells are involved in osteoclast formation. Endocrinology 123, 2600–2602 (1988).
60. Udagawa, N. et al. Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function. Endocrinology 141, 3478–3484 (2000).
61. Miyamoto, T. et al. An adherent condition is required for formation of multinuclear osteoclasts in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor kappa B ligand. Blood 96, 4335–4343 (2000).
62. Itoh, Y. Membrane-type matrix metalloproteinases: Their functions and regulations. Matrix Biol. 44–46, 207–223 (2015).
63. Nakashima, T. et al. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat. Med. 17, 1231–1234 (2011).
64. Xiong, J. et al. Matrix-embedded cells control osteoclast formation. Nat. Med. 17, 1235–1241 (2011).
65. Uemura, H. et al. Circulating profiles of osteoprotegerin and soluble receptor activator of nuclear factor κB ligand in post-menopausal women. J. Endocrinol. Invest. 31, 163–168 (2008).
66. Nakamura, T. et al. Estrogen Prevents Bone Loss via Estrogen Receptor α and Induction of Fas Ligand in Osteoclasts. Cell 130, 811–823 (2007).
67. Proell, V. et al. Orchiectomy upregulates free soluble RANKL in bone marrow of aged rats. Bone 45, 677–681 (2009).
68. Geusens, P. P. et al. The ratio of circulating osteoprotegerin to RANKL in early rheumatoid arthritis predicts later joint destruction. Arthritis Rheum. 54, 1772–1777 (2006).
69. van Tuyl, L. H. D. et al. Baseline RANKL:OPG ratio and markers of bone and cartilage degradation predict annual radiological progression over 11 years in rheumatoid arthritis. Ann. Rheum. Dis. 69, 1623–1628 (2010).
70. Jung, K. & Lein, M. Bone turnover markers in serum and urine as diagnostic, prognostic and monitoring biomarkers of bone metastasis. Biochim. Biophys. Acta - Rev. Cancer 1846, 425–438 (2014).
71. Kraj, M. et al. Correlation of osteoprotegerin and sRANKL concentrations in serum and bone marrow of multiple myeloma patients. Arch. Immunol. Ther. Exp. (Warsz). 53, 454–64 (2005).
72. Todenhöfer, T. et al. Serum receptor activator of nuclear factor κb ligand (RANKL) levels predict biochemical recurrence in patients undergoing radical prostatectomy. BJU Int. 113, 152–159 (2014).
73. Kendler, D. L. et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J. Bone Miner. Res. 25, 72–81 (2010).
74. Stopeck, A. T. et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: A randomized, double-blind study. J. Clin. Oncol. 28, 5132–5139 (2010).
75. Fizazi, K. et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: A randomised, double-blind study. Lancet 377, 813–822 (2011).
76. Henry, D. H. et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J. Clin. Oncol. 29, 1125–1132 (2011).
77. Smyth, M. J., Yagita, H. & Mcarthur, G. A. Combination anti-CTLA-4 and Anti-RANKL in metastatic melanoma. J. Clin. Oncol. 32, e104–e106 (2014).
78. Diarra, D. et al. Dickkopf-1 is a master regulator of joint remodeling. Nat. Med. 13, 156–163 (2007).
79. Bostwick, A. D., Salama, A. K. & Hanks, B. A. Rapid complete response of metastatic melanoma in a patient undergoing ipilimumab immunotherapy in the setting of active ulcerative colitis. J. Immunother. Cancer 3, (2015).
80. Liede, A. et al. An observational study of concomitant immunotherapies and denosumab in patients with advanced melanoma or lung cancer. Oncoimmunology 1–11 (2018). doi:10.1080/2162402X.2018.1480301
81. Ahern, E. et al. Co-administration of RANKL and CTLA4 antibodies enhances lymphocyte-mediated antitumor immunity in mice. Clin. Cancer Res. 23, 5789–5801 (2017).
82. Ahern, E. et al. RANKL blockade improves efficacy of PD1-PD-L1 blockade or dual PD1-PD-L1 and CTLA4 blockade in mouse models of cancer. Oncoimmunology 7, (2018).
83. Afzal, M. Z. & Shirai, K. Immune checkpoint inhibitor (anti-CTLA-4, anti-PD-1) therapy alone versus immune checkpoint inhibitor (anti-CTLA-4, anti-PD-1) therapy in combination with anti-RANKL denosumuab in malignant melanoma: A retrospective analysis at a tertiary care center. Melanoma Res. 28, 341–347 (2018).
84. Nakai, Y. et al. Efficacy of an orally active small-molecule inhibitor of RANKL in bone metastasis. Bone Res. 7, 1 (2019).
85. Nagashima, K. et al. Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota. Nat. Immunol. 18, 675–682 (2017).
86. Roodman, G. D. & Dougall, W. C. RANK ligand as a therapeutic target for bone metastases and multiple myeloma. Cancer Treat. Rev. 34, 92–101 (2008).
87. Esposito, M., Guise, T. & Kang, Y. The biology of bone metastasis. Cold Spring Harb. Perspect. Med. 8, (2018).
88. Croucher, P. I., McDonald, M. M. & Martin, T. J. Bone metastasis: The importance of the neighbourhood. Nat. Rev. Cancer 16, 373–386 (2016).
89. Morrison, S. J. & Scadden, D. T. The bone marrow niche for haematopoietic stem cells. Nature 505, 327–334 (2014).
90. Bottos, A. et al. Decreased NK-cell tumour immunosurveillance consequent to JAK inhibition enhances metastasis in breast cancer models. Nat. Commun. 7, (2016).
91. Xiong, J. et al. Soluble RANKL contributes to osteoclast formation in adult mice but not ovariectomy-induced bone loss. Nature Communications 9, (2018).
92. Honma, M. et al. RANKL subcellular trafficking and regulatory mechanisms in osteocytes. J. Bone Miner. Res. 28, 1936–1949 (2013).
93. Cappariello, A. et al. Osteoblast-Derived Extracellular Vesicles Are Biological Tools for the Delivery of Active Molecules to Bone. J. Bone Miner. Res. 33, 517–533 (2018).
94. Qi, W.-X. et al. Incidence and risk of denosumab-related hypocalcemia in cancer patients: a systematic review and pooled analysis of randomized controlled studies. Curr. Med. Res. Opin. 29, 1067–1073 (2013).
95. Chen, Y. T., Levasseur, R., Vaishnav, S., Karsenty, G. & Bradley, A. Bigenic Cre/loxP, puDeltatk conditional genetic ablation. Nucleic Acids Res. 32, (2004).
96. Chen, L. M. et al. RANKL increases migration of human lung cancer cells through intercellular adhesion molecule-1 up-regulation. J. Cell. Biochem. 112, 933–941 (2011).
97. Palafox, M. et al. RANK induces epithelial-mesenchymal transition and stemness in human mammary epithelial cells and promotes tumorigenesis and metastasis. Cancer Res. 72, 2879– 2888 (2012).
98. Irshad, S. et al. RORγt+ innate lymphoid cells promote lymph node metastasis of breast cancers. Cancer Res. 77, 1083–1096 (2017).
99. Walsh, N. C. et al. Activated human T cells express alternative mRNA transcripts encoding a secreted form of RANKL. Genes Immun. 14, 336–345 (2013).
論文の公開元へ
