rank ligand


Summary: A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.

Top Publications

  1. Dai J, Lu Y, Roca H, Keller J, Zhang J, McCauley L, et al. Immune mediators in the tumor microenvironment of prostate cancer. Chin J Cancer. 2017;36:29 pubmed publisher
    ..This review highlights the concept that immune cells and cytokines offer a potentially promising target for prostate cancer therapy. ..
  2. Frodge B, Ebersole J, Kryscio R, Thomas M, Miller C. Bone remodeling biomarkers of periodontal disease in saliva. J Periodontol. 2008;79:1913-9 pubmed
  3. Urano Morisawa E, Takami M, Suzawa T, Matsumoto A, Osumi N, Baba K, et al. Induction of osteoblastic differentiation of neural crest-derived stem cells from hair follicles. PLoS ONE. 2017;12:e0174940 pubmed publisher
    ..These results suggest that NC-derived hair follicle cells possess a capacity for osteoblastic differentiation and may be useful for developing new bone regenerative medicine therapies. ..
  4. Boman A, Kokkonen H, Arlestig L, Berglin E, Rantapaa Dahlqvist S. Receptor activator of nuclear factor kappa-B ligand (RANKL) but not sclerostin or gene polymorphisms is related to joint destruction in early rheumatoid arthritis. Clin Rheumatol. 2017;36:1005-1012 pubmed publisher
  5. Xi L, Cao H, Chen Y. OPG/RANK/RANKL axis in atrial fibrillation. Cardiology. 2013;125:174-5 pubmed publisher
  6. Yamakawa Y, Tazawa H, Hasei J, Osaki S, Omori T, Sugiu K, et al. Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction. Cancer Sci. 2017;108:1870-1880 pubmed publisher
    ..These results suggest that combination therapy of OBP-301 and ZOL suppresses osteosarcoma progression via suppression of MCL1 and osteoclast activation. ..
  7. Sato F, Toi M. [Molecular targeted therapy and genomic evolution of breast cancer]. Nihon Rinsho. 2015;73:1364-72 pubmed
    ..In this article, latest knowledge regarding breast cancer genome, especially in terms of 'evolution', is summarized. ..
  8. Knevel R, de Rooy D, Saxne T, Lindqvist E, Leijsma M, Daha N, et al. A genetic variant in osteoprotegerin is associated with progression of joint destruction in rheumatoid arthritis. Arthritis Res Ther. 2014;16:R108 pubmed publisher
    ..35x10-4). This variant was also significant after Bonferroni correction. These results indicate that a genetic variant in OPG is associated with a more severe rate of joint destruction in RA. ..
  9. Elmusrati A, Pilborough A, Khurram S, Lambert D. Cancer-associated fibroblasts promote bone invasion in oral squamous cell carcinoma. Br J Cancer. 2017;117:867-875 pubmed publisher
    ..This study is the first to describe a functional role for CAFs in bone invasion and turnover, identifying a novel potential therapeutic target and diagnostic indicator in this difficult to treat bone invasive malignancy. ..

More Information


  1. Kurihara C, Tanaka T, Yamanouchi D. Hyperglycemia attenuates receptor activator of NF-?B ligand-induced macrophage activation by suppressing insulin signaling. J Surg Res. 2017;214:168-175 pubmed publisher
    ..These data suggest that HG suppressed macrophage activation, through attenuation of glucose uptake via the suppression of the membrane translocation of Glut1 and insulin signaling. ..
  2. Nagashima M, Takahashi H, Shimane K, Nagase Y, Wauke K. Osteogenesis and osteoclast inhibition in rheumatoid arthritis patients treated with bisphosphonates alone or in combination with pitavastatin over an 18-month follow-up after more than 4 years of treatment with bisphosphonates. Arthritis Res Ther. 2012;14:R224 pubmed publisher
    ..Cardiovascular disease is highly prevalent in RA patients and some patients are prescribed statins and bisphosphonate. Bis + statin may confer more benefit to the bone metabolism of these patients compared to Bis alone. ..
  3. Logothetis C. Treatment of prostate cancer metastases: more than semantics. Lancet. 2012;379:4-6 pubmed publisher
  4. Silbermann R, Bolzoni M, Storti P, Guasco D, Bonomini S, Zhou D, et al. Bone marrow monocyte-/macrophage-derived activin A mediates the osteoclastogenic effect of IL-3 in multiple myeloma. Leukemia. 2014;28:951-4 pubmed publisher
  5. Thomas D, Carriere P, Jacobs I. Safety of denosumab in giant-cell tumour of bone. Lancet Oncol. 2010;11:815 pubmed publisher
  6. Qin Y, Peng Y, Zhao W, Pan J, Ksiezak Reding H, Cardozo C, et al. Myostatin inhibits osteoblastic differentiation by suppressing osteocyte-derived exosomal microRNA-218: A novel mechanism in muscle-bone communication. J Biol Chem. 2017;292:11021-11033 pubmed publisher
  7. Goettsch C, Babelova A, Trummer O, Erben R, Rauner M, Rammelt S, et al. NADPH oxidase 4 limits bone mass by promoting osteoclastogenesis. J Clin Invest. 2013;123:4731-8 pubmed
    ..Thus, NOX4 is involved in bone loss and represents a potential therapeutic target for the treatment of osteoporosis. ..
  8. Sliwicka E, Cisoń T, Kasprzak Z, Nowak A, Pilaczyńska Szcześniak Ł. Serum irisin and myostatin levels after 2 weeks of high-altitude climbing. PLoS ONE. 2017;12:e0181259 pubmed publisher
  9. Anastasilakis A, Makras P. Multiple clinical vertebral fractures following denosumab discontinuation. Osteoporos Int. 2016;27:1929-30 pubmed publisher
  10. Shim K, Kim T, Ha H, Lee K, Cho C, Kim H, et al. Lactobacillus fermentation enhances the inhibitory effect of Hwangryun-haedok-tang in an ovariectomy-induced bone loss. BMC Complement Altern Med. 2013;13:106 pubmed publisher
    ..These results suggest that fermented HRT might have the beneficial potential on osteoporosis by inhibiting osteoclastogenesis. ..
  11. Mathiesen I, Salem M, Gerstoft J, Gaardbo J, Obel N, Pedersen C, et al. Complete manuscript Title: Changes in RANKL during the first two years after cART initiation in HIV-infected cART naïve adults. BMC Infect Dis. 2017;17:262 pubmed publisher
    ..Clinical-Trial.gov . id NCT00135460 , August 25, 2005. The study was approved by the Danish Data Protection Agency, Danish Medicines Agency and Regional Ethics Committee. ..
  12. Park O, Kim J, Yang J, Yun C, Han S. Muramyl Dipeptide, a Shared Structural Motif of Peptidoglycans, Is a Novel Inducer of Bone Formation through Induction of Runx2. J Bone Miner Res. 2017;32:1455-1468 pubmed publisher
    ..In conclusion, we suggest that MDP is a novel inducer of bone formation that could potentially be a new therapeutic molecule to protect against osteoporosis. © 2017 American Society for Bone and Mineral Research. ..
  13. Choe J, Park K, Park S, Lee S, Kim S. Regulatory effect of calcineurin inhibitor, tacrolimus, on IL-6/sIL-6R-mediated RANKL expression through JAK2-STAT3-SOCS3 signaling pathway in fibroblast-like synoviocytes. Arthritis Res Ther. 2013;15:R26 pubmed publisher
    ..These data suggest that tacrolimus might affect the RANKL expression in IL-6 stimulated FLS through STAT3 suppression, together with up-regulation of SOCS3. ..
  14. . Denosumab. Limited efficacy in fracture prevention, too many adverse effects. Prescrire Int. 2011;20:145-8 pubmed
    ..In practice, denosumab is not sufficiently effective to outweigh its established and potential risks in postmenopausal osteoporotic women or in castrated men with prostate cancer. ..
  15. Bergdolt S, Kovtun A, Hägele Y, Liedert A, Schinke T, Amling M, et al. Osteoblast-specific overexpression of complement receptor C5aR1 impairs fracture healing. PLoS ONE. 2017;12:e0179512 pubmed publisher
    ..Additional trauma significantly impaired fracture healing, particularly in Col1a1-C5aR1 mice. In conclusion, the data indicate that C5aR1 signaling in osteoblasts plays a detrimental role in bone regeneration after fracture. ..
  16. Hutami I, Izawa T, Mino Oka A, Shinohara T, Mori H, Iwasa A, et al. Fas/S1P1 crosstalk via NF-?B activation in osteoclasts controls subchondral bone remodeling in murine TMJ arthritis. Biochem Biophys Res Commun. 2017;490:1274-1281 pubmed publisher
    ..Thus, the present results suggest that Fas/S1P1 signaling via activation of NF-?B in osteoclast precursor cells is a key factor in the pathogenesis of RA in the TMJ. ..
  17. Hiramatsu R, Ubara Y, Sawa N, Hoshino J, Hasegawa E, Kawada M, et al. Denosumab for low bone mass in hemodialysis patients: a noncontrolled trial. Am J Kidney Dis. 2015;66:175-7 pubmed publisher
  18. Vezzani G, Quartesan S, Cancellara P, Camporesi E, Mangar D, Bernasek T, et al. Hyperbaric oxygen therapy modulates serum OPG/RANKL in femoral head necrosis patients. J Enzyme Inhib Med Chem. 2017;32:707-711 pubmed publisher
    ..HBOT significantly reduced lesion size in all stage I and II patients and in 2 of 11 stage III patients. HBOT increased serum OPG levels but receptor activator of nuclear factor kappa-B ligand (RANKL) levels did not change. ..
  19. Wang Y, van Assen A, Reis C, Setroikromo R, van Merkerk R, Boersma Y, et al. Novel RANKL DE-loop mutants antagonize RANK-mediated osteoclastogenesis. FEBS J. 2017;284:2501-2512 pubmed publisher
    ..The generation of RANK-antagonists is a promising strategy for the exploration of new therapeutics against osteoporosis. ..
  20. Thomas R, Guise T, Yin J, Elliott J, Horwood N, Martin T, et al. Breast cancer cells interact with osteoblasts to support osteoclast formation. Endocrinology. 1999;140:4451-8 pubmed
  21. Choi E, Lee J, Baek S, Kim S. Gene expression profile altered by orthodontic tooth movement during healing of surgical alveolar defect. Am J Orthod Dentofacial Orthop. 2017;151:1107-1115 pubmed publisher
    ..It would be a basis on selecting putative genes to be therapeutically applied for tissue-friendly accelerated orthodontics in the future. ..
  22. Zhu S, Yuan C, Liu Z, Li X, Wang P. [The mechanism of corticotomy accelerating orthodontic tooth movement in SD rats]. Shanghai Kou Qiang Yi Xue. 2017;26:12-16 pubmed
    ..Expression of RANKL in pressure side also increased in Cort group at the 3 and 7 day. Corticotomy accelerates OTM in rats and it may result from promoted bone resorption via increased RANKL expression in periodontal tissue. ..
  23. Chypre M, Madel M, Chaloin O, Blin Wakkach C, Morice C, Mueller C. Porphyrin Derivatives Inhibit the Interaction between Receptor Activator of NF-?B and Its Ligand. ChemMedChem. 2017;12:1697-1702 pubmed publisher
    ..Denosumab, a human monoclonal antibody that blocks the RANK ligand (RANKL), is approved for the treatment of osteoporosis and bone metastasis...
  24. Nagashima K, Sawa S, Nitta T, Tsutsumi M, Okamura T, Penninger J, et al. Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota. Nat Immunol. 2017;18:675-682 pubmed publisher
    ..Thus, the subepithelial mesenchymal cells that serve as M cell inducers have a fundamental role in the maintenance of intestinal immune homeostasis. ..
  25. Garcia Gomez A, Li T, Kerick M, Català Moll F, Comet N, Rodriguez Ubreva J, et al. TET2- and TDG-mediated changes are required for the acquisition of distinct histone modifications in divergent terminal differentiation of myeloid cells. Nucleic Acids Res. 2017;45:10002-10017 pubmed publisher
    ..We demonstrate a novel role of these enzymes in the establishment of specific elements of identity and function in terminal myeloid differentiation...
  26. Nagy E, Lei Y, Martínez Martínez E, Body S, Schlotter F, Creager M, et al. Interferon-? Released by Activated CD8+ T Lymphocytes Impairs the Calcium Resorption Potential of Osteoclasts in Calcified Human Aortic Valves. Am J Pathol. 2017;187:1413-1425 pubmed publisher
    ..CD8+ cell-derived IFN-? suppresses osteoclast function and may thus favor calcification in CAVD. ..
  27. Zhang X, Song Y, Song N, Zhang L, Wang Y, Li D, et al. Rankl expression predicts poor prognosis in gastric cancer patients: results from a retrospective and single-center analysis. Braz J Med Biol Res. 2018;51:e6265 pubmed publisher
    ..000). Together, our results revealed that high expression of RANKL could predict worse outcomes in gastric cancer especially combined with RANK detection, and thereby this pathway could be a useful prognostic indicator of gastric cancer. ..
  28. Park B, Song H, Kwon J, Cho S, Jang S, Kim M, et al. Effects of Salvia miltiorrhiza extract with supplemental liquefied calcium on osteoporosis in calcium-deficient ovariectomized mice. BMC Complement Altern Med. 2017;17:545 pubmed publisher
    ..This result implies the possibility of a pharmacological intervention specifically directed toward a disease such as osteoporosis where decreased bone strength increases the risk of a broken bone . ..
  29. Tao Y, Wang Z, Wang L, Shi J, Guo X, Zhou W, et al. Downregulation of miR-106b attenuates inflammatory responses and joint damage in collagen-induced arthritis. Rheumatology (Oxford). 2017;56:1804-1813 pubmed publisher
    ..Moreover, miR-106b inhibitor treatment suppressed RANK ligand (RANKL) expression, increased osteoprotegerin (OPG) expression and reduced the RANKL:OPG ratio in CIA mice...
  30. Bao C, Liu Y, Sun X, Xing C, Zeng L, Sun G. Periploca forrestii saponin ameliorates CIA via suppressing proinflammatory cytokines and nuclear factor kappa-B pathways. PLoS ONE. 2017;12:e0176672 pubmed publisher
    ..Therefore, PFS is a promising therapeutic alternative for the treatment of RA, evidencing the need to conduct further studies that can identify their active components in treating and preventing RA. ..
  31. Zhao X, Chen L, Wang Z. Aesculin modulates bone metabolism by suppressing receptor activator of NF-?B ligand (RANKL)-induced osteoclastogenesis and transduction signals. Biochem Biophys Res Commun. 2017;488:15-21 pubmed publisher
    ..Taken together, our data demonstrate that AES can modulate bone metabolism by suppressing osteoclastogenesis and related transduction signals. AES therefore could be a promising agent for the treatment of osteoporosis. ..
  32. Uehara N, Kukita A, Kyumoto Nakamura Y, Yamaza T, Yasuda H, Kukita T. Osteoblast-derived Laminin-332 is a novel negative regulator of osteoclastogenesis in bone microenvironments. Lab Invest. 2017;97:1235-1244 pubmed publisher
    ..These findings suggest that Lm-332 produced by osteoblasts in bone tissues has a pivotal role in controlling normal bone remodeling through suppressing osteoclastogenesis. ..
  33. Zhu C, Lingkai S. [Effects of paeonol on the function of bone marrow-derived macrophage from Porphyromonas gingivalis-induced mice]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2017;35:139-144 pubmed publisher
    ..01???????????????BMM?????????TRAP??????????????BMM????????Western blot?????????TRAP?RANK?????????????? ???????????????????????BMM????TNF-??IL-1??IL-6????????????????. ..
  34. Spanoudakis E, Papoutselis M, Terpos E, Dimopoulos M, Tsatalas C, Margaritis D, et al. Overexpression of RANKL by invariant NKT cells enriched in the bone marrow of patients with multiple myeloma. Blood Cancer J. 2016;6:e500 pubmed publisher
  35. Brabnikova Maresova K, Jarosova K, Pavelka K, Stepan J. Serum sclerostin in high-activity adult patients with juvenile idiopathic arthritis. Arthritis Res Ther. 2014;16:460 pubmed publisher
  36. Kobayashi K, Takahashi N, Jimi E, Udagawa N, Takami M, Kotake S, et al. Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med. 2000;191:275-86 pubmed
    ..TNF-alpha together with IL-1alpha may play an important role in bone resorption of inflammatory bone diseases. ..
  37. Aghaloo T, Felsenfeld A, Tetradis S. Osteonecrosis of the jaw in a patient on Denosumab. J Oral Maxillofac Surg. 2010;68:959-63 pubmed publisher
  38. Ke K, Sul O, Chung S, Suh J, Choi H. Lack of NOD2 attenuates ovariectomy-induced bone loss via inhibition of osteoclasts. J Endocrinol. 2017;235:85-96 pubmed publisher
    ..Our data suggest that NOD2 contributes to bone loss in estrogen deficiency by elevating ROS levels in OCs. ..
  39. Murakami K, Kobayashi Y, Uehara S, Suzuki T, Koide M, Yamashita T, et al. A Jak1/2 inhibitor, baricitinib, inhibits osteoclastogenesis by suppressing RANKL expression in osteoblasts in vitro. PLoS ONE. 2017;12:e0181126 pubmed publisher
    ..Hence, Jak1 and Jak2 represent novel therapeutic targets for osteoporosis as well as inflammatory bone diseases including rheumatoid arthritis. ..
  40. Kim J, Lee E, Lee E, Lee Y, Yoo H, Choi J, et al. Atorvastatin inhibits osteoclastogenesis by decreasing the expression of RANKL in the synoviocytes of rheumatoid arthritis. Arthritis Res Ther. 2012;14:R187 pubmed publisher
    ..These results suggest that atorvastatin inhibits osteoclastogenesis and bone destruction in RA patients. ..
  41. Kambayashi Y, Fujimura T, Furudate S, Asano M, Kakizaki A, Aiba S. The Possible Interaction between Receptor Activator of Nuclear Factor Kappa-B Ligand Expressed by Extramammary Paget Cells and its Ligand on Dermal Macrophages. J Invest Dermatol. 2015;135:2547-2550 pubmed publisher
  42. Spirlandeli A, Dick de Paula I, Zamarioli A, Jorgetti V, Ramalho L, Nogueira Barbosa M, et al. Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment. Clinics (Sao Paulo). 2017;72:231-237 pubmed publisher
    ..Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice. ..
  43. van der Heijden L, van de Sande M, Hogendoorn P, Gelderblom H, Dijkstra P. Neoadjuvant denosumab for extensive giant cell tumor in os ischium: a case report. Acta Orthop. 2015;86:393-5 pubmed publisher
  44. Davis H, Pacheco Costa R, Atkinson E, Brun L, Gortazar A, Harris J, et al. Disruption of the Cx43/miR21 pathway leads to osteocyte apoptosis and increased osteoclastogenesis with aging. Aging Cell. 2017;16:551-563 pubmed publisher
    ..These findings identify a novel Cx43/miR21/HMGB1/RANKL pathway involved in preventing osteocyte apoptosis that also controls osteoclast formation/recruitment and is impaired with aging. ..
  45. Kotake S, Nanke Y, Yago T, Kawamoto M, Yamanaka H. Human osteoclastogenic T cells and human osteoclastology. Arthritis Rheum. 2009;60:3158-63 pubmed publisher
  46. Yeo C, Kang W, Seong S, Cho S, Lee H, Yoon Y, et al. Neuromedin B and its receptor silencing suppresses osteoclast generation by modulating precursor proliferation via M-CSF/c-Fms/D-type cyclins. Exp Cell Res. 2017;359:112-119 pubmed publisher
    ..In summary, our study demonstrates that the NMB/NMBR axis plays a pivotal role in osteoclast generation by modulating the proliferation and survival of osteoclast lineage cells. ..
  47. Cao F, Liu X, Cao X, Wang S, Fu K, Zhao Y, et al. Fibroblast growth factor 21 plays an inhibitory role in vascular calcification in vitro through OPG/RANKL system. Biochem Biophys Res Commun. 2017;491:578-586 pubmed publisher
    ..FGF21 inhibited VSMCs calcification via OPG/RANKL system, and through P38 andPI3K/AKT pathways. ..
  48. Okamatsu N, Sakai N, Karakawa A, Kouyama N, Sato Y, Inagaki K, et al. Biological effects of anti-RANKL antibody administration in pregnant mice and their newborns. Biochem Biophys Res Commun. 2017;491:614-621 pubmed publisher
    ..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. ..
  49. Bartold P, Cantley M, Haynes D. Mechanisms and control of pathologic bone loss in periodontitis. Periodontol 2000. 2010;53:55-69 pubmed publisher
  50. Irtyuga O, Malashicheva A, Zhiduleva E, Freylikhman O, Rotar O, Bäck M, et al. NOTCH1 Mutations in Aortic Stenosis: Association with Osteoprotegerin/RANK/RANKL. Biomed Res Int. 2017;2017:6917907 pubmed publisher
    ..i>Conclusion. Our results suggest that the OPG/RANKL/RANK system might be directly influenced by genetic variants of NOTCH1 in aortic valve calcification. ..
  51. El Khassawna T, Merboth F, Malhan D, Bocker W, Daghma D, Stoetzel S, et al. Osteocyte Regulation of Receptor Activator of NF-?B Ligand/Osteoprotegerin in a Sheep Model of Osteoporosis. Am J Pathol. 2017;187:1686-1699 pubmed publisher
    ..The findings of this study can contribute to further explain the success of sclerostin antibodies in treating osteoporotic patients despite increased osteocyte-expressed RANKL. ..
  52. Chinetti Gbaguidi G, Daoudi M, Rosa M, Vinod M, Louvet L, Copin C, et al. Human Alternative Macrophages Populate Calcified Areas of Atherosclerotic Lesions and Display Impaired RANKL-Induced Osteoclastic Bone Resorption Activity. Circ Res. 2017;121:19-30 pubmed publisher
    ..These results indicate that macrophages surrounding calcium deposits in human atherosclerotic plaques are phenotypically defective being unable to resorb calcification. ..
  53. Arioka M, Takahashi Yanaga F, Tatsumoto N, Sasaguri T. Inorganic phosphate-induced impairment of osteoclast cell-cell fusion by the inhibition of AP-1-mediated DC-STAMP expression. Biochem Biophys Res Commun. 2017;493:9-13 pubmed publisher
    ..These results suggested that hyperphosphatemia in the patients with CKD suppresses bone resorption by inhibiting osteoclastogenesis, and this impairs the regulation of bone metabolism. ..
  54. Wang Z, Liu N, Zhou G, Shi T, Wang Z, Gan J, et al. Expression of XBP1s in fibroblasts is critical for TiAl6 V4 particle-induced RANKL expression and osteolysis. J Orthop Res. 2017;35:752-759 pubmed publisher
    ..2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:752-759, 2017. ..
  55. Maria S, Swanson M, Enderby L, D Amico F, Enderby B, Samsonraj R, et al. Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal ost. Aging (Albany NY). 2017;9:256-285 pubmed publisher
    ..In adipose-derived human MSCs, MSDK induced osteoblastogenesis. These findings provide both clinical and mechanistic support for the use of MSDK for the prevention or treatment of osteopenia, osteoporosis or other bone-related diseases...
  56. Atkins G, Haynes D, Graves S, Evdokiou A, Hay S, Bouralexis S, et al. Expression of osteoclast differentiation signals by stromal elements of giant cell tumors. J Bone Miner Res. 2000;15:640-9 pubmed
    ..Thus GCT constitutively express all of the signals that are currently understood to be necessary for the differentiation of osteoclasts from precursor cells. ..
  57. Fan Y, Hanai J, Le P, Bi R, Maridas D, DeMambro V, et al. Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate. Cell Metab. 2017;25:661-672 pubmed publisher
    ..These studies reveal an important mechanism for PTH's therapeutic action through its ability to direct mesenchymal cell fate. ..
  58. Yao Z, Lei W, Duan R, Li Y, Luo L, Boyce B. RANKL cytokine enhances TNF-induced osteoclastogenesis independently of TNF receptor associated factor (TRAF) 6 by degrading TRAF3 in osteoclast precursors. J Biol Chem. 2017;292:10169-10179 pubmed publisher
    ..These findings suggest that preventing TRAF3 degradation with drugs like chloroquine could reduce excessive OC formation in diseases in which bone resorption is increased in response to elevated production of these cytokines. ..
  59. Gillooly K, Pulicicchio C, Pattoli M, Cheng L, Skala S, Heimrich E, et al. Bruton's tyrosine kinase inhibitor BMS-986142 in experimental models of rheumatoid arthritis enhances efficacy of agents representing clinical standard-of-care. PLoS ONE. 2017;12:e0181782 pubmed publisher
    ..The results suggest BMS-986142 represents a potential therapeutic for clinical investigation in RA, as monotherapy or co-administered with agents with complementary mechanisms of action. ..
  60. Irtiuga O, Zhiduleva E, Dubrovskaia O, Moiseeva O. [Concentration of osteoprotegerin and RANKL in blood serum of patients with aortic stenosis]. Kardiologiia. 2014;54:44-8 pubmed
    ..The data obtained correspond to the conception of importance of OPG/RANKL/RANK system activation for development and progression of degenerative aortic stenosis. ..
  61. Hsiao H, Wu J, Lin W. (-)-Epicatechin 3-O-?-D-allopyranoside prevent ovariectomy-induced bone loss in mice by suppressing RANKL-induced NF-?B and NFATc-1 signaling pathways. BMC Complement Altern Med. 2017;17:245 pubmed publisher
    ..Overall, our findings suggested that ECAP suppresses RANKL-induced osteoclastogenesis through NF-?B and NFATc-1 signaling pathways, and has the potential for use in osteoporosis treatment. ..
  62. Fan L, Wang Q, Liu R, Zong M, He D, Zhang H, et al. Citrullinated fibronectin inhibits apoptosis and promotes the secretion of pro-inflammatory cytokines in fibroblast-like synoviocytes in rheumatoid arthritis. Arthritis Res Ther. 2012;14:R266 pubmed publisher
    ..Furthermore, cFn increased the secretion of TNF-? and IL-1 by FLSs. cFn plays a potential pathophysiologic role in RA by inhibiting apoptosis and increasing proinflammatory cytokine secretion of FLSs. ..
  63. Ozaki Y, Koide M, Furuya Y, Ninomiya T, Yasuda H, Nakamura M, et al. Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis. PLoS ONE. 2017;12:e0184904 pubmed publisher
    ..Taken together, W9 may be a useful drug to prevent alveolar bone loss in periodontitis. ..
  64. Okamoto K, Nakashima T, Shinohara M, Negishi Koga T, Komatsu N, Terashima A, et al. Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems. Physiol Rev. 2017;97:1295-1349 pubmed publisher
    ..The concept of a unified osteoimmune system will be absolutely indispensable for basic and translational approaches to diseases related to bone and/or the immune system. ..
  65. Dimitrova P, Ivanovska N, Belenska L, Milanova V, Schwaeble W, Stover C. Abrogated RANKL expression in properdin-deficient mice is associated with better outcome from collagen-antibody-induced arthritis. Arthritis Res Ther. 2012;14:R173 pubmed publisher
  66. Wei C, You F, Mei L, Jian S, Qiang C. Total glucosides of paeony prevents juxta-articular bone loss in experimental arthritis. BMC Complement Altern Med. 2013;13:186 pubmed publisher
    ..The decreased RANKL and increased OPG expression seen in TGP treated animals could explain how administration of TGP maintains higher BMD. ..
  67. Brownlow N, Mol C, Hayford C, Ghaem Maghami S, Dibb N. Dasatinib is a potent inhibitor of tumour-associated macrophages, osteoclasts and the FMS receptor. Leukemia. 2009;23:590-4 pubmed publisher
  68. Araújo A, Pereira A, Medeiros C, Brito G, Leitao R, Araújo L, et al. Effects of metformin on inflammation, oxidative stress, and bone loss in a rat model of periodontitis. PLoS ONE. 2017;12:e0183506 pubmed publisher
    ..Metformin, at a concentration of 50 mg/kg, decreases the inflammatory response, oxidative stress and bone loss in ligature-induced periodontitis in rats. ..
  69. Ganesan R, Rasool M. Interleukin 17 regulates SHP-2 and IL-17RA/STAT-3 dependent Cyr61, IL-23 and GM-CSF expression and RANKL mediated osteoclastogenesis by fibroblast-like synoviocytes in rheumatoid arthritis. Mol Immunol. 2017;91:134-144 pubmed publisher
    ..Taken together, our findings demonstrate that IL-17 regulates SHP-2 expression and IL-17RA/STAT-3 dependent production of Cyr61, IL-23, GM-CSF and RANKL in AA-FLS and may reveal a new insight into the pathogenesis of RA. ..
  70. Kim J, Lee J, Lee G, Noh E, Song H, Gu D, et al. Sophorae Flos extract inhibits RANKL-induced osteoclast differentiation by suppressing the NF-?B/NFATc1 pathway in mouse bone marrow cells. BMC Complement Altern Med. 2017;17:164 pubmed publisher
    ..SFE attenuated the RANKL-mediated induction of NF-?B through inhibition of I?B? phosphorylation, which contributed to inhibiting of RANKL-induced osteoclast differentiation through downregulation of NFATc1. ..
  71. Nakamura S, Koyama T, Izawa N, Nomura S, Fujita T, Omata Y, et al. Negative feedback loop of bone resorption by NFATc1-dependent induction of Cadm1. PLoS ONE. 2017;12:e0175632 pubmed publisher
    ..These results suggest that Cadm1 is a direct target of NFATc1, which is induced by RANKL through epigenetic modification, and regulates osteoclastic bone resorption in a negative feedback manner. ..
  72. Wisitrasameewong W, Kajiya M, Movila A, Rittling S, Ishii T, Suzuki M, et al. DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption. J Dent Res. 2017;96:685-693 pubmed publisher
    ..Therefore, it is plausible that a novel therapeutic regimen targeting DC-STAMP could suppress periodontal bone loss. ..
  73. Granchi D, Torreggiani E, Massa A, Caudarella R, Di Pompo G, Baldini N. Potassium citrate prevents increased osteoclastogenesis resulting from acidic conditions: Implication for the treatment of postmenopausal bone loss. PLoS ONE. 2017;12:e0181230 pubmed publisher
    ..These data provide the biological basis for the use of K citrate in preventing the osteopenia progression resulting from low-grade acidosis. ..
  74. Mizoguchi F, Murakami Y, Saito T, Miyasaka N, Kohsaka H. miR-31 controls osteoclast formation and bone resorption by targeting RhoA. Arthritis Res Ther. 2013;15:R102 pubmed
    ..miR-31 controls cytoskeleton organization in osteoclasts for optimal bone resorption activity by regulating the expression of RhoA. ..
  75. Trawitzki B, Lilge L, de Figueiredo F, Macedo A, Issa J. Low-intensity laser therapy efficacy evaluation in mice subjected to acute arthritis condition. J Photochem Photobiol B. 2017;174:126-132 pubmed publisher
    ..05). LILT showed signs of an anti-inflammatory effect when applied once, but promoted increased resorptive area when used for two sessions, indicating the importance of a controlled LILT protocol to reach therapeutic effects. ..
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