Kong, Y.Y. et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397, 315–323 (1999).
Hanada, R., Hanada, T., Sigl, V., Schramek, D. & Penninger, J.M. RANKL/RANK-beyond bones. J. Mol. Med. 89, 647–656 (2011).
Fata, J.E. et al. The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development. Cell 103, 41–50 (2000).
Jones, D.H. et al. Regulation of cancer cell migration and bone metastasis by RANKL. Nature 440, 692–696 (2006).
Gonzalez-Suarez, E. et al. RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis. Nature 468, 103–107 (2010).
Tan, W. et al. Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling. Nature 470, 548–553 (2011).
Schramek, D. et al. Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer. Nature 468, 98–102 (2010).
Kiechl, S. et al. Blockade of receptor activator of nuclear factor-κB (RANKL) signaling improves hepatic insulin resistance and prevents development of diabetes mellitus. Nat. Med. 19, 358–363 (2013).
Hanada, R. et al. Central control of fever and female body temperature by RANKL/RANK. Nature 462, 505–509 (2009).
Simonet, W.S. et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89, 309–319 (1997).
Lacey, D.L. et al. Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab. Nat. Rev. Drug Discov. 11, 401–419 (2012).
Weng, J. et al. Deletion of G protein-coupled receptor 48 leads to ocular anterior segment dysgenesis (ASD) through down-regulation of Pitx2. Proc. Natl. Acad. Sci. USA 105, 6081–6086 (2008).
Luo, J. et al. Regulation of bone formation and remodeling by G-protein-coupled receptor 48. Development 136, 2747–2756 (2009).
Carmon, K.S., Gong, X., Lin, Q., Thomas, A. & Liu, Q. R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling. Proc. Natl. Acad. Sci. USA 108, 11452–11457 (2011).
de Lau, W. et al. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature 476, 293–297 (2011).
Styrkarsdottir, U. et al. Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits. Nature 497, 517–520 (2013).
Abe, E. et al. TSH is a negative regulator of skeletal remodeling. Cell 115, 151–162 (2003).
Sun, L. et al. FSH directly regulates bone mass. Cell 125, 247–260 (2006).
Du, B. et al. Lgr4/Gpr48 negatively regulates TLR2/4-associated pattern recognition and innate immunity by targeting CD14 expression. J. Biol. Chem. 288, 15131–15141 (2013).
Wang, Y. et al. Lgr4 regulates mammary gland development and stem cell activity through the pluripotency transcription factor Sox2. Stem Cells 31, 1921–1931 (2013).
Wang, J. et al. Ablation of LGR4 promotes energy expenditure by driving white-to-brown fat switch. Nat. Cell Biol. 15, 1455–1463 (2013).
Gao, Y. et al. Up-regulation of GPR48 induced by down-regulation of p27Kip1 enhances carcinoma cell invasiveness and metastasis. Cancer Res. 66, 11623–11631 (2006).
Wu, J. et al. GPR48, a poor prognostic factor, promotes tumor metastasis and activates β-catenin/TCF signaling in colorectal cancer. Carcinogenesis 34, 2861–2869 (2013).
Joshi, P.A. et al. RANK signaling amplifies WNT-responsive mammary progenitors through R-SPONDIN1. Stem Cell Reports 5, 31–44 (2015).
Wang, D. et al. Structural basis for R-spondin recognition by LGR4/5/6 receptors. Genes Dev. 27, 1339–1344 (2013).
Deng, C. et al. Multi-functional norrin is a ligand for the LGR4 receptor. J. Cell Sci. 126, 2060–2068 (2013).
Tang, X. et al. GPR116, an adhesion G-protein-coupled receptor, promotes breast cancer metastasis via the Gαq-p63RhoGEF-Rho GTPase pathway. Cancer Res. 73, 6206–6218 (2013).
Clapham, D.E. Calcium signaling. Cell 131, 1047–1058 (2007).
Wu, X. et al. RANKL regulates Fas expression and Fas-mediated apoptosis in osteoclasts. J. Bone Miner. Res. 20, 107–116 (2005).
Krönke, G. et al. R-spondin 1 protects against inflammatory bone damage during murine arthritis by modulating the Wnt pathway. Arthritis Rheum. 62, 2303–2312 (2010).
Moon, J.B. et al. Akt induces osteoclast differentiation through regulating the GSK3β/NFATc1 signaling cascade. J. Immunol. 188, 163–169 (2012).
Takeshita, S. et al. Osteoclast-secreted CTHRC1 in the coupling of bone resorption to formation. J. Clin. Invest. 123, 3914–3924 (2013).
Mizuno, A. et al. Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. Biochem. Biophys. Res. Commun. 247, 610–615 (1998).
Lacey, D.L. et al. Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Am. J. Pathol. 157, 435–448 (2000).
Jimi, E. et al. Osteoclast differentiation factor acts as a multifunctional regulator in murine osteoclast differentiation and function. J. Immunol. 163, 434–442 (1999).
Boyce, B.F. Advances in the regulation of osteoclasts and osteoclast functions. J. Dent. Res. 92, 860–867 (2013).
Manolagas, S.C. & Parfitt, A.M. What old means to bone. Trends Endocrinol. Metab. 21, 369–374 (2010).
Pierce, B.G., Hourai, Y. & Weng, Z. Accelerating protein docking in ZDOCK using an advanced 3D convolution library. PLoS One 6, e24657 (2011).
Dai, W. et al. Improvement in low-homology template-based modeling by employing a model evaluation method with focus on topology. PLoS One 9, e89935 (2014).
Li, C. et al. Maslinic acid suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss by regulating RANKL-mediated NF-κB and MAPK signaling pathways. J. Bone Miner. Res. 26, 644–656 (2011).
Chu, G.C. et al. RANK- and c-Met-mediated signal network promotes prostate cancer metastatic colonization. Endocr. Relat. Cancer 21, 311–326 (2014).
Wu, X. et al. Caffeic acid 3,4-dihydroxy-phenethyl ester suppresses receptor activator of NF-κB ligand–induced osteoclastogenesis and prevents ovariectomy-induced bone loss through inhibition of mitogen-activated protein kinase/activator protein 1 and Ca2+–nuclear factor of activated T-cells cytoplasmic 1 signaling pathways. J. Bone Miner. Res. 27, 1298–1308 (2012).
McMichael, B.K., Meyer, S.M. & Lee, B.S. c-Src-mediated phosphorylation of thyroid hormone receptor-interacting protein 6 (TRIP6) promotes osteoclast sealing zone formation. J. Biol. Chem. 285, 26641–26651 (2010).
Zhang, Z. et al. Ferroportin1 deficiency in mouse macrophages impairs iron homeostasis and inflammatory responses. Blood 118, 1912–1922 (2011).