Function
(From Uniprot) |
Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy. Induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca (2+) resulting in the activation of NFATC1, which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation.
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| Gene References into Functions |
- The results demonstrate that the membrane-bound form of RANKL is sufficient for most functions of this protein but that the soluble form does contribute to physiological bone remodeling in adult mice. PMID: 30046091
- the molecular level, we confirmed, for the first time, that RES upregulated FoxO1 transcriptional activity by inhibiting the PI3K/AKT signaling pathway, and hence promoted resistance to oxidative damage and restrained osteoclastogenesis. Inhibition of the PI3K/AKT signaling pathway may be induced by RANKL. PMID: 29115382
- Deletion of the RANKL D5 enhancer delays the progression of atherosclerotic plaque development and plaque calcification in hypercholesterolemic mice. PMID: 28419519
- these results suggest that A2BAR stimulation inhibits the activation of ERK1/2, p38 and NF-kappaB by RANKL, which suppresses the induction of osteoclast marker genes, thus contributing to the decrease in osteoclast cell-cell fusion and bone resorption activity. PMID: 29047264
- compressive force induced the differentiation of RAW264.7 from increase in RANK and decrease in LGR4 expression. PMID: 29572179
- miR-145 expression was inhibited in RANKL-induced osteoclastogenesis PMID: 29577879
- LPS increased mRNA and protein expressions of IL-6 and RANKL on day 14 PMID: 28637991
- hBD-1 potentiates the induction of in vitro osteoclastogenesis by RANKL via enhanced phosphorylation of the p44/42 MAPKs PMID: 28709835
- In conclusion, the results suggest that linarin has anti-osteoclastic effects and may serve as potential modulatory agents for the prevention and treatment of bone loss-associated diseases. PMID: 29269297
- Rankl(-/-) bone marrow-mesenchymal stromal cell displayed reduced clonogenicity and osteogenic capacity. PMID: 28100034
- In this study, the authors identified by gene expression profiling that microgravity induces high levels of TRAIL expression in murine preosteoclast cells in the absence of RANKL stimulation compared to ground based cultures. PMID: 27142480
- These results suggest that LOX has the ability to induce RANKL expression on stromal cells; however, it fails to substitute for RANKL in osteoclastogenesis. PMID: 27606829
- Results demonstrated picroside II strongly inhibited RANKL-induced osteoclast formation when added during the early stage of BMMs cultures, suggesting that it acts on osteoclast precursors to inhibit RANKL/RANK signaling. PMID: 28464271
- loss of BMP signaling specifically in osteocytes dramatically increases bone mass presumably through simultaneous inhibition of RANKL and SOST, leading to osteoclast inhibition and Wnt activation together. PMID: 27402532
- The potentiation of RANKL induced CTX release by dexamethasone was significantly less in bone marrow macrophage cells from mice with conditional knockout of the osteoclastic glucocorticoid receptor and completely absent in cells from GR(dim) mice, which carry a point mutation in one dimerizing interface of the GC receptor. PMID: 27596806
- findings demonstrate that mTORC1 activation-stimulated RANKL expression in B cells is sufficient to induce bone loss and osteoporosis. The study also established a link between mTORC1 and the RANKL/OPG axis via negative regulation of beta-catenin. PMID: 26825871
- dihydroartemisinin inhibited RANKL-induced NF-kappaB and NFAT activity. PMID: 26684711
- Cyanidin chloride is capable of inhibiting osteoclast formation, hydroxyapatite resorption and RANKL-induced signal pathways in vitro and ovariectomy-induced bone loss in vivo. PMID: 28771720
- Together these data indicate that osteocyte apoptosis plays a central and controlling role in triggering osteocyte RANKL production and the activation of new resorption leading to bone loss in disuse. PMID: 26852281
- data suggest that, particularly with combination treatment of zoledronic acid (ZA) and glucocorticoids, surviving lymphocytes might be the source of inflammation-induced sRANKL. Thus, circulating sRANKL levels might be modulated by ZA. PMID: 26999703
- matrine abrogated RANKL-induced activation of NF-kappaB, AKT, and MAPK pathways and suppressed osteoclastogenesis-related marker expression, including matrix metalloproteinase 9, NFATc1, TRAP, C-Src, and cathepsin K PMID: 28739641
- The anti-osteoclastic and anti-resorptive actions of Luteoloside are mediated via blocking NFATc1 activity and the attenuation of RANKL-mediated Ca(2+) signaling as well as NF-kappaB and MAPK pathways. PMID: 28681916
- Osteoprotegerin facilitates pulmonary arterial hypertension pathogenesis by regulating pulmonary arterial smooth muscle cell proliferation via integrin alphavbeta3/FAK/AKT signaling pathway. PMID: 28077433
- results demonstrate that IL-15 and RANKL induce osteoclastogenesis synergistically, and IL-15 might play a novel and major role in destructive inflammatory bone diseases PMID: 27608420
- Absence of Musashi2 in osteoclast precursors promotes apoptosis and inhibits RANKL-induced NF-kappaB activation, which is essential for osteoclast survival. PMID: 27441652
- This study demonstrates that Col6a1-Cre driver mice are as useful as Twist2-Cre driver mice for functional analyses of GALT-resident mesenchymal cells, including MCi cells. PMID: 28882590
- Estrogens and androgens inhibit osteoblast-driven osteoclastogenesis through non-genomic mechanism(s) that entail, MMP-mediated RANKL dissociation from the cell membrane. PMID: 28213978
- sRANKL increased macrophage glucose uptake at normal glucose concentrations, which was impaired by hyperglycemia pretreatment through the inhibition of Glut1 membrane translocation and the insulin receptor and IRS-1 gene transcription. PMID: 28624040
- Our findings show that anti-RANKL antibody administration during pregnancy results in not only an undesirable increase in bone mass, but also has harmful effects on newborn survival. PMID: 28760341
- RANKL represses the transcription of the E3 ubiquitin ligase RNF146 through an NF-kappaB-related inhibitory element in the RNF146 promoter. PMID: 28287403
- This study showed that RANKL favors osteoclastogenesis via attenuation of Nrf2-mediated antioxidant enzyme expression by competing with Bach1 nuclear accumulation. PMID: 27836987
- Membrane-bound RANKL induces M cell differentiation and CCL20 expression in the follicle associated epithelium of gut-associated lymphoid tissues. PMID: 28436956
- The data show that S. aureus enhances bone resorption and periosteal osteoclast formation by increasing osteoblast RANKL production through TLR2. PMID: 27311019
- Data (including data from studies using knockout mice) suggest that RANKL enhances TNF-induced osteoclast formation from precursor spleen cells and enhances bone resorption independently of Traf6 by degrading Traf3, a known inhibitor of osteoclastogenesis. (RANKL = osteoclast differentiation factor; TNF = tumor necrosis factor; Traf = TNF receptor-associated factor) PMID: 28438834
- Results suggest that MAPK signaling pathway is necessary for receptor activator of nuclear factor kappa-B ligand (RANKL) expression in bone marrow stromal cell. PMID: 28161637
- endocortical resorption is driven by reduced osteoprotegerin rather than elevated RANKL expression PMID: 27460899
- The results showed that AG490 inhibited (p)-JAK2 and RANKL expression. PMID: 28278513
- Play a supportive role in the RANKL-dependent differentiation. PMID: 27413168
- increased expression of RANKL in heterogeneous bone marrow cells provoked bone destruction during Group A Streptococcus infection. PMID: 26894505
- beta-lapachone inhibits RANKL-induced osteoclastogenesis and could be considered a potent inhibitor of RANKL-mediated bone diseases PMID: 27913299
- differentiation by suppressing the Ca(2+)-calcineurin-NFATc1 signaling pathway. Although many questions remain unresolved, to our knowledge, this is the first report demonstrating that PEMF is beneficial against RANKL-dependent osteoclastic differentiation in RAW264.7 cells in vitro via inhibiting the Ca(2+)-calcineurin-NFATc1 signaling pathway. PMID: 27856256
- these results demonstrate that RANKL expressed by osteocytes is required for the bone loss as well as the increase in B cell number caused by estrogen deficiency. PMID: 27733688
- In conclusion, the present study demonstrated that EA can suppress osteoclastogenesis in vitro. Moreover, we clarified that these inhibitory effects of EA occur through suppression of NF-kappaB and ERK activation. Therefore, EA may be a potential agent in the treatment of osteoclast-related diseases such as osteoporosis. PMID: 27349866
- MDH1 expression was induced by receptor activator of nuclear factor kappa-B ligand (RANKL) treatment. PMID: 27179783
- miR-338-3p may play a significant role in glucocorticoid-induced osteoclast differentiation and function by targeting RANKL in osteoclasts. PMID: 27706599
- the protein and RNA levels of RANKLinduced cFos and nuclear factor of activated T-cell cytoplasmic 1 were suppressed by centipedegrass extract (CGE). These results indicated that CGE may serve as a useful drug in the prevention of bone loss. PMID: 27035226
- Lipopolysaccharides significantly up-regulated RANKL expression and activated the ERK1/2 pathway to induce IL-6 mRNA expression and protein synthesis in MLO-Y4 cells. PMID: 27778412
- this study shows that OPG constitutes an early biomarker with in experimental model od severe malaria PMID: 26766771
- Osteoprotegerin plays a role in preserving myocardial structure and function with ageing through a reduction in apoptosis and preservation of the matrix structure PMID: 26825553
- These results indicate that activation of Panx1 and P2X7 R are required for apoptotic osteocytes in fatigued bone to trigger RANKL production in neighboring bystander osteocytes and implicate ATP as an essential signal mediating this process. PMID: 26553756
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| Involvement in disease |
Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes. |
