References
Okamoto, K. et al. Osteoimmunology: the conceptual framework unifying the immune and skeletal systems. Physiol. Rev. 97, 1295–1349 (2017).
Kong, Y. Y. et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397, 315–323 (1999).
Walsh, M. C. & Choi, Y. Biology of the RANKL-RANK-OPG system in immunity, bone, and beyond. Front. Immunol. 5, 1–11 (2014).
Sigl, V., Jones, L. P. & Penninger, J. M. RANKL/RANK: from bone loss to the prevention of breast cancer. Open Biol. 6, 160230 (2016).
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).
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).
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).
Xiong, J. et al. Soluble RANKL contributes to osteoclast formation in adult mice but not ovariectomy-induced bone loss. Nat. Commun. 9, 2909 (2018).
Nagashima, K. et al. Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota. Nat. Immunol. 18, 675–682 (2017).
Fata, J. E. et al. The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development. Cell 103, 41–50 (2000).
Nakashima, T. et al. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat. Med. 17, 1231–1234 (2011).
Xiong, J. et al. Matrix-embedded cells control osteoclast formation. Nat. Med. 17, 1235–1241 (2011).
Danks, L. et al. RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation. Ann. Rheum. Dis. 75, 1187–1195 (2016).
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).
Guerrini, M. M. et al. Inhibition of the TNF family cytokine RANKL prevents autoimmune inflammation in the central nervous system. Immunity 43, 1174–1185 (2015).
Lacey, D. L. et al. Osteoprotegrin ligand is cytokine that regulates osteoclast differentiation and activation. Cell 93, 165–176 (1998).
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. USA 95, 3597–3602 (1998).
Takahashi, N. et al. Osteoblastic cells are involved in osteoclast formation. Endocrinology 123, 2600–2602 (1988).
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 κB ligand. Blood 96, 4335–4343 (2000).
CAS PubMed Google Scholar
Udagawa, N. et al. Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function. Endocrinology 141, 3478–3484 (2000).
Findlay, D. M. & Atkins, G. J. Relationship between serum RANKL and RANKL in bone. Osteoporos. Int. 22, 2597–2602 (2011).
Tsukasaki, M. et al. Host defense against oral microbiota by bone-damaging T cells. Nat. Commun. 9, 1–11 (2018).
Onder, L. et al. Lymphatic endothelial cells control initiation of lymph node organogenesis. Immunity 47, 80–92.e4 (2017).
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).
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).
Croucher, P. I., McDonald, M. M. & Martin, T. J. Bone metastasis: the importance of the neighbourhood. Nat. Rev. Cancer 16, 373–386 (2016).
Esposito, M., Guise, T. & Kang, Y. The biology of bone metastasis. Cold Spring Harb. Perspect. Med. 8, a031252 (2018).
Jones, D. H. et al. Regulation of cancer cell migration and bone metastasis by RANKL. Nature 440, 692–696 (2006).
Sanchez-Sweatman, O. H., Lee, J., Or, F. W. & Singh, G. Direct osteolysis induced by metastatic murine melanoma cells: role of matrix metalloproteinases. Eur. J. Cancer 33, 918–925 (1997).
Nakai, Y. et al. Efficacy of an orally active small-molecule inhibitor of RANKL in bone metastasis. Bone Res. 7, 1 (2019).
Nakamura, M. et al. Osteoprotegerin regulates bone formation through a coupling mechanism with bone resorption. Endocrinology 144, 5441–5449 (2003).
Seeman, E. & Delmas, P. D. Bone quality—the material and structural basis of bone strength and fragility. N. Engl. J. Med. 354, 2250–2261 (2006).
Kramer, I. et al. Osteocyte Wnt/β-catenin signaling is required for normal bone homeostasis. Mol. Cell. Biol. 30, 3071–3085 (2010).
Ominsky, M. S. et al. RANKL inhibition with osteoprotegerin increases bone strength by improving cortical and trabecular bone architecture in ovariectomized rats. J. Bone Miner. Res. 23, 672–682 (2008).
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).
Rachner, T. D. et al. Prognostic value of RANKL/OPG serum levels and disseminated tumor cells in nonmetastatic breast cancer. Clin. Cancer Res. 25, 1369–1378 (2019).
