The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index.
Osteoclast differentiation and activation
Abstract
Osteoclasts are specialized cells derived from the monocyte/macrophage haematopoietic lineage that develop and adhere to bone matrix, then secrete acid and lytic enzymes that degrade it in a specialized, extracellular compartment. Discovery of the RANK signalling pathway in the osteoclast has provided insight into the mechanisms of osteoclastogenesis and activation of bone resorption, and how hormonal signals impact bone structure and mass. Further study of this pathway is providing the molecular basis for developing therapeutics to treat osteoporosis and other diseases of bone loss.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Because TRAIL and RANKL are known to regulate osteoclast differentiation and survival (33–35), these findings suggest that increased RANK (tumor necrosis factor receptor superfamily member 11a) signaling may be involved in the regulation of bone growth and remodeling induced by ACVR2B/Fc.”
From Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight (2020) · cites this paper as [33]
In the citing paper
“Because TRAIL and RANKL are known to regulate osteoclast differentiation and survival (33–35), these findings suggest that increased RANK (tumor necrosis factor receptor superfamily member 11a) signaling may be involved in the regulation of bone growth and remodeling induced by ACVR2B/Fc.”
From Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight (2020) · cites this paper as [33]
Citations
Cites
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
Lacey, D. L., Timms, E., Tan, H.-L., Kelley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81569-x · Cited by 5,439
Self-citationOsteoprotegerin: a novel secreted protein involved in the regulation of bone density.
Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M.-S., Lüthy, R., Nguyen, H. Q., Wooden, S., Bennett, L., Boone, T., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80209-3 · Cited by 5,130
Self-citationYasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S.-I., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3597 · Cited by 4,224
Bone Resorption by Osteoclasts
Teitelbaum, S. L. (2000) · Science · doi:10.1126/science.289.5484.1504 · Cited by 3,962
OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis.
Kong, Y.-Y., Yoshida, H., Sarosi, I., Tan, H.-L., Timms, E., Capparelli, C., Morony, S., Oliveira-dos-Santos, A. J., Van, G., Itie, A., et al. (1999) · Nature · doi:10.1038/16852 · Cited by 3,351
Self-citationTakayanagi, H., Kim, S., Koga, T., Nishina, H., Isshiki, M., Yoshida, H., Saiura, A., Isobe, M., Yokochi, T., Inoue, J.-I., et al. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00369-6 · Cited by 2,701
Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
Bucay, N., Sarosi, I., Dunstan, C. R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H. L., Xu, W., Lacey, D. L., et al. (1998) · Genes & Development · doi:10.1101/gad.12.9.1260 · Cited by 2,483
Self-citationNF-κB in cancer: from innocent bystander to major culprit
Karin, M., Cao, Y., Greten, F. R., & Li, Z. (2002) · Nature reviews. Cancer · doi:10.1038/nrc780 · Cited by 2,476
A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function.
Anderson, D. M., Maraskovsky, E., Billingsley, W. L., Dougall, W. C., Tometsko, M. E., Roux, E. R., Teepe, M. C., DuBose, R. F., Cosman, D., & Galibert, L. (1997) · Nature · doi:10.1038/36593 · Cited by 2,290
Kong, Y.-Y., Feige, U., Sarosi, I., Bolon, B., Tafuri, A., Morony, S., Capparelli, C., Li, J., Elliott, R., McCabe, S., et al. (1999) · Nature · doi:10.1038/46303 · Cited by 1,856
Self-citation
Cited by
Sorted by citations
Items 101–200 of 1,034
Pathogenesis of bone disease in multiple myeloma: from bench to bedside
Terpos, E., Ntanasis-Stathopoulos, I., Gavriatopoulou, M., & Dimopoulos, M. A. (2018) · Blood Cancer Journal · doi:10.1038/s41408-017-0037-4 · Cited by 354
The role of the immune system in the pathophysiology of osteoporosis
Clowes, J. A., Riggs, B. L., & Khosla, S. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00334.x · Cited by 366
RANKL-induced DC-STAMP Is Essential for Osteoclastogenesis
Kukita, T., Wada, N., Kukita, A., Kakimoto, T., Sandra, F., Toh, K., Nagata, K., Iijima, T., Horiuchi, M., Matsusaki, H., et al. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040518 · Cited by 357
“Receptor activator of NF- B ligand (RANKL) is now known as an essential cytokine for the osteoclastogenesis, and downstream signaling events mediated by its receptor RANK have been studied extensively (3, 4).”
BackgroundEffects of denosumab on fracture and bone mineral density by level of kidney function
Jamal, S. A., Ljunggren, Ö., Stehman‐Breen, C. O., Cummings, S. R., McClung, M. R., Goemaere, S., Ebeling, P. R., Franek, E., Yang, Y., Egbuna, O. I., et al. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.403 · Cited by 357
“By blocking the binding of RANKL to RANK, denosumab decreases the number and activity of osteoclasts, decreases bone resorption, and increases bone mineral density (BMD).((9,10)) In postmenopausal women with osteoporosis, as compared with placebo, 36 months of denosumab treatment significantly increased spine, hip, an…”
BackgroundEstrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival
Krum, S. A., Miranda‐Carboni, G. A., Hauschka, P. V., Carroll, J. S., Lane, T. F., Freedman, L. P., & Brown, M. A. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601984 · Cited by 361
“…Way, Cambridge CB2 0RE, UK The EMBO Journal (2008) 27, 535–545 | & 2008 European Molecular Biology Organization |All Rights Reserved 0261-4189/08 www.embojournal.org &2008 European Molecular Biology Organization The EMBO Journal VOL 27 | NO 3 | 2008 EMBO THE JOURNAL 535 (M-CSF) (Boyle et al, 2003).”
BackgroundA road map for understanding molecular and genetic determinants of osteoporosis
Yang, T.-L., Shen, H., Liu, A., Dong, S.-S., Zhang, L., Deng, F.-Y., Zhao, Q., & Deng, H.-W. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0282-7 · Cited by 341
Calcineurin/NFAT Signaling in Osteoblasts Regulates Bone Mass
Winslow, M. M., Pan, M., Starbuck, M. W., Gallo, E. M., Deng, L., Karsenty, G., & Crabtree, G. R. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.04.006 · Cited by 355
Bone Remodeling in Post-menopausal Osteoporosis
Lerner, U. H. (2006) · Journal of Dental Research · doi:10.1177/154405910608500703 · Cited by 354
Papapoulos, S. E., Chapurlat, R. D., Libanati, C. R., Brandi, M. L., Brown, J. P., Czerwinski, E. J., Krieg, M.-A., Man, Z., Mellström, D., Radominski, S., et al. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1479 · Cited by 345
“Receptor activator of NF-kB (RANK) ligand plays an essential role in mediating resorption through osteoclast formation, function, and survival.((1,2)) Denosumab is a fully human monoclonal antibody that inhibits RANK ligand.”
BackgroundBone tissue regeneration: biology, strategies and interface studies
Ansari, M. (2019) · Progress in Biomaterials · doi:10.1007/s40204-019-00125-z · Cited by 353
Probiotics Protect Mice from Ovariectomy-Induced Cortical Bone Loss
Ohlsson, C., Engdahl, C., Fåk, F., Andersson, A., Windahl, S. H., Farman, H. H., Movérare-Skrtic, S., Islander, U., & Sjögren, K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092368 · Cited by 339
“TNFa promotes osteoclastogenesis indirectly by stimulating RANKL expression by marrow stromal cells and osteoblasts and by direct stimulation of OCL precursors exposed to permissive levels of RANKL [32–34].”
BackgroundInfluentialBone marrow cells in the ‘pre-metastatic niche’: within bone and beyond
Kaplan, R. N., Psaila, B., & Lyden, D. C. (2006) · Cancer and Metastasis Reviews · doi:10.1007/s10555-006-9036-9 · Cited by 344
“Derived from hematopoietic precursors, osteoclasts require RANKL (receptor activator of NF-κB ligand) signals from osteoblasts for their proliferation, differentiation and bone-resorbing activity [70].”
BackgroundSerum leptin level is a regulator of bone mass
Elefteriou, F., Takeda, S., Ebihara, K., Magré, J., Patano, N., Kim, C. A., Ogawa, Y., Liu, X., Ware, S. M., Craigen, W. J., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308744101 · Cited by 335
The new bone biology: Pathologic, molecular, and clinical correlates
Cohen, M. M. (2006) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31368 · Cited by 340
Goody, P. R., Hosen, M. R., Christmann, D., Niepmann, S. T., Zietzer, A., Adam, M., Bönner, F., Zimmer, S., Nickenig, G., & Jansen, F. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.313067 · Cited by 358
WD40 repeat domain proteins: a novel target class?
Schapira, M., Tyers, M., Torrent, M., & Arrowsmith, C. H. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.179 · Cited by 335
Hydrogen peroxide is essential for estrogen-deficiency bone loss and osteoclast formation.
Lean, J., Jagger, C., Kirstein, B., Fuller, K., & Chambers, T. (2005) · Endocrinology · doi:10.1210/en.2004-1021 · Cited by 346
OsteoMacs: Key players around bone biomaterials
Miron, R. J., & Bosshardt, D. D. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.12.017 · Cited by 328
“Macrophages and bone resorbing osteoclasts are closely related however can be distinguished by the presence of additional nuclei in osteoclasts as well as morphological features and expression of marker proteins later discussed [19,93].”
Bioinspired surface modification of orthopedic implants for bone tissue engineering
Hu, C. Q., Ashok, D., Nisbet, D. R., & Gautam, V. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119366 · Cited by 330
Rivollier, A., Mazzorana, M., Tebib, J. G., Piperno, M., Aitsiselmi, T., Rabourdin‐Combe, C., Jurdic, P., & Delprat, C. (2004) · Blood · doi:10.1182/blood-2004-01-0041 · Cited by 323
Pathogenesis of myeloma bone disease
Roodman, G. D. (2009) · Leukemia · doi:10.1038/leu.2008.336 · Cited by 398
Molecular and epigenetic basis of macrophage polarized activation
Porta, C., Riboldi, E., Ippolito, A., & Sica, A. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2015.10.003 · Cited by 334
Lewiecki, E. M., Miller, P. D., McClung, M. R., Cohen, S. B., Bolognese, M. A., Liu, Y., Wang, A., Siddhanti, S., & Fitzpatrick, L. A. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070809 · Cited by 319
“RANK, the receptor for RANKL, has been identified on the surface of osteoclasts at several stages of differentiation, including prefusion osteoclasts and mature osteoclasts.((5,7))”
BackgroundTanaka, S., Nakamura, K., Takahasi, N., & Suda, T. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00327.x · Cited by 325
“Osteoclasts are specifically differentiated for bone resorption (8, 11).”
BackgroundReactive Oxygen Species Stimulates Receptor Activator of NF-κB Ligand Expression in Osteoblast
Bai, X., Lü, D., Liu, A., Zhang, Z., Li, X., Zou, Z., Zeng, W., Cheng, B.-L., & Luo, S.-Q. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m409332200 · Cited by 323
Ryu, J., Kim, H. J., Chang, E., Huang, H., Banno, Y., & Hong‐Hee, K. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601430 · Cited by 332
“RANKL binding to its cognate receptor RANK leads to recruitment of adaptor proteins TRAFs (TNF receptor-associated factors) (Lee and Kim, 2003; Boyle et al, 2003; Teitelbaum and Ross, 2003).”
BackgroundInfluentialSignal integration and diversification through the p62 scaffold protein
Moscat, J., Díaz-Meco, M. T., & WOOTEN, M. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.12.002 · Cited by 315
RANKL/RANK/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling
Tobeiha, M., Moghadasian, M. H., Amin, N., & Jafarnejad, S. (2020) · BioMed Research International · doi:10.1155/2020/6910312 · Cited by 309
“In fact, several agents that induce RANKL influence OPG regulation [61, 62].”
BackgroundCurrent concepts in the biology of orthodontic tooth movement
Masella, R. S., & Meister, M. (2006) · American Journal of Orthodontics and Dentofacial Orthopedics · doi:10.1016/j.ajodo.2005.12.013 · Cited by 307
Cytokine responses against periodontal infection: protective and destructive roles
Liu, Y.-C. G., Lerner, U. H., & Teng, Y.-T. A. (2009) · Periodontology 2000 · doi:10.1111/j.1600-0757.2009.00321.x · Cited by 308
Physiology of Bone Formation, Remodeling, and Metabolism
Kini, U., & Nandeesh, B. N. (2012) · Springer eBooks · doi:10.1007/978-3-642-02400-9_2 · Cited by 318
Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification
Doherty, T. M., Fitzpatrick, L. A., Inoue, D., Qiao, J.-H., Fishbein, M. C., Detrano, R., Shah, P. K., & Rajavashisth, T. B. (2004) · Endocrine Reviews · doi:10.1210/er.2003-0015 · Cited by 299
“M-CSF is a key cytokine involved in survival of osteoclast progenitors and differentiation toward a mature functional osteoclast phenotype (157, 158, 229, 270).”
BackgroundPeriodontal Disease: Linking the Primary Inflammation to Bone Loss
Benedetto, A. D., Gigante, I., Colucci, S. C., & Grano, M. (2013) · Clinical and Developmental Immunology · doi:10.1155/2013/503754 · Cited by 300
“IL-17 exerts its osteoclastogenic activity by enhancing RANKL expression on osteoblasts and CD4+ T cells [56].”
Model structure and control of bone remodeling: A theoretical study
Pivonka, P., Zimak, J., Smith, D. W., Gardiner, B. S., Dunstan, C. R., Sims, N. A., Martin, T. J., & Mundy, G. R. (2008) · Bone · doi:10.1016/j.bone.2008.03.025 · Cited by 303
“Important physiological effects for many bone diseases including osteoporosis, Paget's disease, tumormetastasis, humoral hypercalcemia of malignancy, and multiple myeloma, can be explained through imbalances in RANKL/OPG ratio [7,12,24,28,29].”
BackgroundInterplay between Cartilage and Subchondral Bone Contributing to Pathogenesis of Osteoarthritis
Sharma, A. R., Jagga, S., Lee, S., & Nam, J. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms141019805 · Cited by 298
“Activation of PAR-2 in OA subchondral osteoblasts plays a role in subchondral bone resorption by increasing the expression of MMP-1, MMP-9, RANKL and IL-6 but not osteoprotegerin or MMP-13.”
BackgroundInfluentialThe role of vitamin D in the endocrinology controlling calcium homeostasis
Fleet, J. C. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.04.008 · Cited by 298
Pathogenesis of myeloma bone disease
Roodman, G. D. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22403 · Cited by 297
“Its expression is induced by cytokines that stimulate bone resorption [Boyle et al., 2003] such as PTH, 1,25 OH Vitamin D3 and prostaglandins [Hofbauer and Heufelder, 1998; Yasuda et al., 1998].”
BackgroundMacrophages: The Road Less Traveled, Changing Anticancer Therapy
Guerriero, J. L. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.03.006 · Cited by 300
In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone Formation
Wittkowske, C., Reilly, G. C., Lacroix, D., & Perrault, C. M. (2016) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2016.00087 · Cited by 310
Yoshitake, F., Itoh, S., Narita, H., Ishihara, K., & Ebisu, S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m607999200 · Cited by 297
The osteoclast: A multinucleated, hematopoietic‐origin, bone‐resorbing osteoimmune cell
Bar‐Shavit, Z. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21553 · Cited by 298
Staphylococcus aureus vs. Osteoblast: Relationship and Consequences in Osteomyelitis
Josse, J., Velard, F., & Gangloff, S. C. (2015) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2015.00085 · Cited by 299
“OPG is a soluble decoy receptor that targets RANK-L to limit osteoclastogenesis (Boyle et al., 2003).”
BackgroundMolecular Mechanisms and Emerging Therapeutics for Osteoporosis
Noh, J., Yang, Y. D., & Jung, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207623 · Cited by 299
“OPG is a decoy receptor of RANKL that competitively binds to the trimer RANKL, preventing RANKL-induced osteoclast maturation and promoting osteoclast apoptosis [15,75].”
BackgroundInfluentialHypercalcemia of malignancy: An update on pathogenesis and management
Mirrakhimov, A. (2015) · North American Journal of Medical Sciences · doi:10.4103/1947-2714.170600 · Cited by 287
“[12-14] In conclusion, the intricate interaction between calcium levels, PTH, Vitamin D, and bone cells regulates bone metabolism and calcium release from the bones.”
Local communication on and within bone controls bone remodeling
Henriksen, K., Neutzsky-Wulff, A. V., Bonewald, L. F., & Karsdal, M. A. (2009) · Bone · doi:10.1016/j.bone.2009.03.671 · Cited by 292
“There is a tight regulation of RANKL, OPG and M-CSF expression by cells of the osteoblastic lineage, often referred to as stromal cells, and a diverse group of substances influences the expression pattern of these molecules [43], thereby affecting bone turnover.”
BackgroundNiche heterogeneity in the bone marrow
Birbrair, A., & Frenette, P. S. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13016 · Cited by 313
Kennedy, O. D., Herman, B. C., Laudier, D. M., Majeska, R. J., Sun, H. B., & Schaffler, M. B. (2012) · Bone · doi:10.1016/j.bone.2012.01.025 · Cited by 275
The Role of the Immune Cells in Fracture Healing
Baht, G. S., Vi, L., & Alman, B. A. (2018) · Current Osteoporosis Reports · doi:10.1007/s11914-018-0423-2 · Cited by 275
Advancing application of mesenchymal stem cell-based bone tissue regeneration
Shang, F., Yu, Y., Liu, S., Ming, L., Zhang, Y., Zhou, Z., Zhao, J., & Jin, Y. J. (2020) · Bioactive Materials · doi:10.1016/j.bioactmat.2020.08.014 · Cited by 293
Biology and Mechanisms of Action of the Vitamin D Hormone
Pike, J. W., & Christakos, S. (2017) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2017.07.001 · Cited by 292
Aging, inflammation, immunity and periodontal disease
Ebersole, J. L., Graves, C. L., González, O. A., Dawson, D. R., Morford, L. A., Emecen‐Huja, P., Hartsfield, J. K., Huja, S. S., Pandruvada, S. N. M., & Wallet, S. M. (2016) · Periodontology 2000 · doi:10.1111/prd.12135 · Cited by 315
“prostaglandin E2, tumor necrosis factor-alpha, interleukin-1beta, interleukin-6 and interleukin-17) appear to play a critical role in enhancing osteoclastogenesis (20), whereas other molecules [e.”
Osteonecrosis of the Jaw in a Patient on Denosumab
Aghaloo, T. L., Felsenfeld, A. L., & Tetradis, S. (2010) · Journal of Oral and Maxillofacial Surgery · doi:10.1016/j.joms.2009.10.010 · Cited by 277
Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy
Ito, H., Koefoed, M., Tiyapatanaputi, P., Gromov, K., Goater, J. J., Carmouche, J. J., Zhang, X., Rubery, P. T., Rabinowitz, J. E., Samulski, R. J., et al. (2005) · Nature Medicine · doi:10.1038/nm1190 · Cited by 272
“In addition to essential nutrients, this blood supply brings in osteoclast precursors that differentiate in response to RANKL expressed by stromal cell”
BackgroundOsteoclast lineage and function
Väänänen, H. K., & Laitala‐Leinonen, T. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.03.037 · Cited by 274
Huang, H., Kim, H. J., Chang, E.-J., Lee, Z. H., Hwang, S. J., Kim, H.-M., Lee, Y.-K., & Kim, H. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.74 · Cited by 290
“In terms of the coupling of bone formation and bone resorption, osteoblasts express both M-CSF and RANKL on their surface, which are the two pivotal cytokines required for osteoclastogenesis.(12,30) Among many human diseases associated with abnormal IL-17 levels, rheumatoid arthritis is of particular interest, because…”
BackgroundFoxO proteins restrain osteoclastogenesis and bone resorption by attenuating H2O2 accumulation
Bartell, S. M., Kim, H., Ambrogini, E., Li, H., Iyer, S. V., Ucer, S., Rabinovitch, P. S., Jilka, R. L., Weinstein, R. S., Zhao, H., et al. (2014) · Nature Communications · doi:10.1038/ncomms4773 · Cited by 272
The Mechanism of Osteoclast Differentiation Induced by IL-1
Kim, J. H., Jin, H. M., Kim, K., Song, I., Youn, B. U., Matsuo, K., & Kim, N. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803007 · Cited by 279
“1, and NF of activated T cells (NFAT) c1, all factors that are known to be important for osteoclastogenesis (1, 3, 10).”
BackgroundNishimura, M., Chiba, M., OHASHI, T., Sato, M., Shimizu, Y., Igarashi, K., & Mitani, H. (2008) · American Journal of Orthodontics and Dentofacial Orthopedics · doi:10.1016/j.ajodo.2006.01.046 · Cited by 268
Skeletal Aging and Osteoporosis: Mechanisms and Therapeutics
Chandra, A., & Rajawat, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073553 · Cited by 281
“Differentiation of osteoclasts require binding of receptor activator of nuclear factor kappa-B (RANK) ligand (RANKL) to the RANK receptor on the osteoclast surface [9,10] together with the secretion of macrophage colony-stimulating factor (M-CSF) by osteoblasts and bone marrow stromal cells [11].”
BackgroundChen, E. H., Grote, E., Mohler, W., & Vignery, A. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.03.033 · Cited by 263
Tumor-Induced Osteoclast miRNA Changes as Regulators and Biomarkers of Osteolytic Bone Metastasis
Ell, B., Mercatali, L., Ibrahim, T., Campbell, N., Schwarzenbach, H., Pantel, K., Amadori, D., & Kang, Y. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.09.008 · Cited by 266
Bai, L., Du, Z., Du, J., Yao, W., Zhang, J., Weng, Z., Liu, S., Zhao, Y., Liu, Y., Zhang, X., et al. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.02.010 · Cited by 265
“Additionally, the conditioned medium fromMFs cultured onMAO450 improves the expression of OPG, which is a decoy receptor for receptor activator of NF-kB ligand (RANKL), exerts a critical role in preventing bone resorption [66].”
BackgroundCytokines and Chemokines in Periodontitis
Ramadan, D. E., Hariyani, N., Indrawati, R., Ridwаn, R. D., & Diyatri, I. (2020) · European Journal of Dentistry · doi:10.1055/s-0040-1712718 · Cited by 275
MafB negatively regulates RANKL-mediated osteoclast differentiation
Kim, K., Kim, J. H., Lee, J., Jin, H. M., Kook, H. Y., Kim, K. K., Lee, S. Y., & Kim, N. (2006) · Blood · doi:10.1182/blood-2006-09-048249 · Cited by 264
Bone regeneration mediated by biomimetic mineralization of a nanofiber matrix
Mata, Á., Geng, Y., Henrikson, K. J., Aparicio, C., Stock, S. R., Satcher, R. L., & Stupp, S. I. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.04.013 · Cited by 260
“Furthermore, this HA-containing nichemay also be stimulating osteoclast activity [51], which would subsequently stimulate osteoblasts to begin the formation of new bone [52].”
BackgroundOrganotropism of Breast Cancer Metastasis
Lü, X., & Kang, Y. (2007) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-007-9047-3 · Cited by 270
“RANKL and OPG can also be secreted by many stromal cells in the bone microenvironment, including fibroblasts, activated T cells or dendritic cells and endothelial cells [19, 20].”
Osteoprotegerin Inhibits Vascular Calcification Without Affecting Atherosclerosis in ldlr (−/−) Mice
Morony, S., Tintut, Y., Zhang, Z., Cattley, R. C., Van, G., Dwyer, D., Stolina, M., Kostenuik, P. J., & Demer, L. L. (2008) · Circulation · doi:10.1161/circulationaha.107.707380 · Cited by 258
The Central Role of Wear Debris in Periprosthetic Osteolysis
Purdue, P. E., Koulouvaris, P., Nestor, B. J., & Sculco, T. P. (2006) · HSS Journal® The Musculoskeletal Journal of Hospital for Special Surgery · doi:10.1007/s11420-006-9003-6 · Cited by 261
“generation and activation [113].”
Akt1 in Osteoblasts and Osteoclasts Controls Bone Remodeling
Kawamura, N., Kugimiya, F., Oshima, Y., Ohba, S., Ikeda, T., Saito, T., Shinoda, Y., Kawasaki, Y., Ogata, N., Hoshi, K., et al. (2007) · PLoS ONE · doi:10.1371/journal.pone.0001058 · Cited by 259
“Many systemic and local factors are involved in the regulation [1,2], among which insulin, insulin-like growth factor-I (IGF-I), bone morphogenetic factors (BMPs), and Wnt proteins are potent bone anabolic factors [3–6].”
BackgroundBone metastasis in prostate cancer: emerging therapeutic strategies
Sturge, J., Caley, M. P., & Waxman, J. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2011.67 · Cited by 262
“This heterotypic cell–cell interaction induces the fusion of preosteoclasts and the formation of mature multinucleated osteoclasts, which are capable of bone resorption ( Figure 1 )”
BackgroundMechanisms and control of pathologic bone loss in periodontitis
Bartold, P. M., Cantley, M. D., & Haynes, D. R. (2010) · Periodontology 2000 · doi:10.1111/j.1600-0757.2010.00347.x · Cited by 252
“Osteoclasts are multinucleated cells that are derived from the monocyte ⁄ macrophage lineage and are considered to be the principal cell responsible for bone resorption (9, 54, 84).”
BackgroundBone, H. G., Chapurlat, R. D., Brandi, M. L., Brown, J. P., Czerwinski, E. J., Krieg, M.-A., Mellström, D., Radominski, S., Reginster, J., Resch, H., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-1597 · Cited by 257
“Receptor activator of nuclear factor- B ligand (RANKL) plays an essential role in mediating bone resorption through osteoclast formation, function, and survival (1, 2).”
BackgroundAkt Induces Osteoclast Differentiation through Regulating the GSK3β/NFATc1 Signaling Cascade
Moon, J. B., Kim, J. H., Kim, K., Youn, B. U., Ko, A., Lee, S. Y., & Kim, N. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101254 · Cited by 259
Bone and the hematopoietic niche: a tale of two stem cells
Bianco, P. (2011) · Blood · doi:10.1182/blood-2011-01-315069 · Cited by 259
McKay, R. R., Kroeger, N., Xie, W., Lee, J., Knox, J. J., Bjarnason, G. A., MacKenzie, M. J., Wood, L. A., Srinivas, S., Vaishampayan, U. N., et al. (2013) · European Urology · doi:10.1016/j.eururo.2013.08.012 · Cited by 253
“Currently approved agents for the prevention of SREs in these patients include zoledronic acid, a potent bisphosphonate, and denosumab, a monoclonal antibody against the receptor activator of nuclear factor-kb ligand, a cytokine important in osteoclast differentiation, activation, and survival [13].”
Piva, R., Ruggeri, B., Williams, M. J., Costa, G., Tamagno, I., Ferrero, D., Giai, V., Coscia, M., Peola, S., Massaia, M., et al. (2007) · Blood · doi:10.1182/blood-2007-07-100651 · Cited by 252
Roles of Mitogen-Activated Protein Kinases in Osteoclast Biology
Lee, K., Seo, I., Choi, M. H., & Jeong, D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103004 · Cited by 258
“Especially, macrophage colony stimulating factor (M-CSF) and receptor activator for nuclear factor κ-B ligand (RANKL) are indispensable in the regulation of the sequential processes of osteoclastogenesis, including osteoclast precursor proliferation, adhesion, migration, and cell-cell fusion to form multinucleated cel…”
BackgroundInfluentialDeng, C., Zhang, Q., He, P., Zhou, B., He, K., Sun, X., Lei, G., Gong, T., & Zhang, Z. (2021) · Nature Communications · doi:10.1038/s41467-021-22454-z · Cited by 252
“13 and 14), thereby demonstrating the recovery of bone function balance.”
InfluentialChen, K., Qiu, P., Yuan, Y. J., Zheng, L., He, J., Wang, C., Guo, Q., Kenny, J., Liu, Q., Zhao, J., et al. (2019) · Theranostics · doi:10.7150/thno.30206 · Cited by 253
“It is widely accepted that excessive osteoclast activity during the regenerative phase, rather than during the necrosis of cells and tissue, directly contributes to the loss of bone integrity and ensuing subchondral bone fracture [6-9].”
BackgroundInfluentialWang, X., Kua, H.-Y., Hu, Y., Guo, K., Zeng, Q., Wu, Q., Ng, H., Karsenty, G., Crombrugghe, B. D., Yeh, J. K., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200507106 · Cited by 254
“It has been well established that osteoblasts control osteoclast differentiation by synthesizing M-CSF, RANKL, and osteoprotegerin (OPG, a RANKL decoy receptor; Suda et al., 1999; Boyle et al., 2003).”
Mechanisms of in Vivo Degradation and Resorption of Calcium Phosphate Based Biomaterials
Sheikh, Z., Abdallah, M., Hanafi, A., Misbahuddin, S., Rashid, H., & Glogauer, M. (2015) · Materials · doi:10.3390/ma8115430 · Cited by 250
“Many growth factors and extracellular matrix proteins are involved in the differentiation and activation of monocyte/macrophage and osteoclast cells [40,46–48].”
BackgroundTashjian, A. H., & Gagel, R. F. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.051023 · Cited by 248
The M-CSF receptor in osteoclasts and beyond
Mun, S. H., Park, P. S. U., & Park‐Min, K. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0484-z · Cited by 257
Kim, K., Kim, J. H., Lee, J., Jin, H., Lee, S., Fisher, D. E., Kook, H. Y., Kim, K. K., Choi, Y., & Kim, N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505815200 · Cited by 247
Vis, M., Havaardsholm, E. A., Haugeberg, G., Uhlig, T., Voskuyl, A. E., van de Stadt, R. J., Dijkmans, B. A. C., Woolf, A. D., Kvien, T. K., & Lems, W. F. (2006) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2005.044198 · Cited by 246
Bone disorders in chronic liver disease
Collier, J. (2007) · Hepatology · doi:10.1002/hep.21852 · Cited by 238
A Phosphorus-Based Dendrimer Targets Inflammation and Osteoclastogenesis in Experimental Arthritis
Hayder, M., Poupot, M., Baron, M., Nigon, D., Turrin, C., Caminade, A., Majoral, J., Eisenberg, R. A., Fournié, J., Cantagrel, A. G., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002212 · Cited by 247
“M-CSF and RANKL signaling acts synergistically with proinflammatory cytokines IL-1b, TNF-a, and IL-17 (50, 51).”
BackgroundInfluentialRole of ITAM‐containing adapter proteins and their receptors in the immune system and bone
Humphrey, M. B., Lanier, L. L., & Nakamura, M. C. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00325.x · Cited by 244
“OCLs are derived from myeloid precursor cells (78); thus, it is likely that they may use similar mechanisms to regulate cellular development and function.”
BackgroundInfluentialLi, H., Hong, S., Qian, J., Zheng, Y., Yang, J., & Yi, Q. (2010) · Blood · doi:10.1182/blood-2009-11-255026 · Cited by 248
Gnant, M., Pfeiler, G., Steger, G. G., Egle, D., Greil, R., Fitzal, F., Wette, V., Balić, M., Haslbauer, F., Melbinger‐Zeinitzer, E., et al. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30862-3 · Cited by 239
Microarchitecture, the key to bone quality
Brandi, M. L. (2009) · Lara D. Veeken · doi:10.1093/rheumatology/kep273 · Cited by 238
Denosumab in the Treatment of Osteoporosis: 10 Years Later: A Narrative Review
Kendler, D. L., Cosman, F., Stad, R. K., & Ferrari, S. (2021) · Advances in Therapy · doi:10.1007/s12325-021-01936-y · Cited by 249
“Adapted from References [20] and [21] thickness, bone density, and ultimately, bone strength [37, 44].”
MethodCao, J., Gregoire, B. R., & Gao, H. (2009) · Bone · doi:10.1016/j.bone.2009.02.017 · Cited by 235
“These cytokines have been shown capable of stimulating osteoclast activity through regulating RANKL/RANK/ OPG pathway [44,45].”
BackgroundMetabolic regulation of osteoclast differentiation and function
Indo, Y., Takeshita, S., Ishii, K., Hoshii, T., Aburatani, H., Hirao, A., & Ikeda, K. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1976 · Cited by 245
“and collagenolytic enzymes, respectively, through the ruffled bordermembrane into the closed space between themembrane and bone surface, where bone degradation actually takes place.((3,4)) As such, bone resorption is an energy‐demanding process, and osteoclasts are assumed to undergo metabolic adaptation during the co…”
BackgroundThe Effect of Inflammation on Bone
Epsley, S., Tadros, S., Farid, A., Kargilis, D., Mehta, S., & Rajapakse, C. S. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2020.511799 · Cited by 252
Destaing, O., Saltel, F., Gilquin, B., Chabadel, A., Khochbin, S., Ory, S., & Jurdic, P. (2005) · Journal of Cell Science · doi:10.1242/jcs.02425 · Cited by 244
“In the presence of M-CSF and RANK-L, monocytemacrophage precursors fuse together to form large multinucleated cells in vitro (Boyle et al., 2003).”
BackgroundOsteocyte control of osteoclastogenesis
O’Brien, C. A., Nakashima, T., & Takayanagi, H. (2012) · Bone · doi:10.1016/j.bone.2012.08.121 · Cited by 251
“Although both cytokines are essential for osteoclastogenesis, M-CSF is primarily involved in stimulating the replication of osteoclast progenitors while RANKL is responsible for stimulating their differentiation [12].”
BackgroundVitamin D status in India--its implications and remedial measures.
Harinarayan, C. V., & Joshi, S. (2009) · PubMed · Cited by 234
Functions of vitamin D in bone
Goltzman, D. (2018) · Histochemistry and Cell Biology · doi:10.1007/s00418-018-1648-y · Cited by 232
“RANKL can bind to its cognate receptor RANK in osteoclasts, and increase osteoclast formation and action (Boyle et al. 2003).”
BackgroundOsteoclast precursors, RANKL/RANK, and immunology
Xing, L., Schwarz, E. M., & Boyce, B. F. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00336.x · Cited by 236
“In contrast to broad expression of RANKL, RANK, the receptor for RANKL, is only identified on mature osteoclasts, dendritic cells, and OCPs (8, 69, 70), which are therefore the major target cells for RANKL and OPG.”
Background
Metadata
- Authors
- Boyle, W. J., Simonet, W. S., & Lacey, D. L.
- Affiliations
- Amgen (United States) (US)
- Corresponding author
- Boyle, William J.
- ORCID
- Boyle, William J.
- Venue
- Nature
- Published
- 2003-05
- Volume
- 423
- Issue
- 6937
- Pages
- 337-342
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2093252878
- Cited by
- 6,670
- References
- 77
- Citations by year
- 2026: 240 · 2025: 269 · 2024: 294 · 2023: 357 · 2022: 349 · 2021: 404 · 2020: 376 · 2019: 381 · 2018: 371 · 2017: 324 · 2016: 311 · 2015: 332 · 2014: 352 · 2013: 315 · 2012: 336
- FWCI
- 11.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Bone and Dental Protein Studies
- Keywords
- osteoclasts, osteoclastogenesis, bone resorption, monocyte/macrophage lineage, bone matrix degradation, hormonal regulation of bone, osteoporosis
- MeSH terms
- Animals, Bone Resorption, Carrier Proteins, Cell Differentiation, Glycoproteins, Humans, Membrane Glycoproteins, Osteoclasts, Osteoporosis, Signal Transduction, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review