Cited by 1,440Bone Metabolism and DiseasesOsteomyelitis and Bone Disorders ResearchRheumatoid Arthritis Research and Therapies

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TNF-α induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand

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Lam, Jonathan, Takeshita, Sunao, Barker, Jane E., Kanagawa, Osami, Ross, F. Patrick, Teitelbaum, Steven L.·2000·Journal of Clinical Investigation

DOI 10.1172/jci11176PMC PMC387259

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Abstract

While TNF-alpha is pivotal to the pathogenesis of inflammatory osteolysis, the means by which it recruits osteoclasts and promotes bone destruction are unknown. We find that a pure population of murine osteoclast precursors fails to undergo osteoclastogenesis when treated with TNF-alpha alone. In contrast, the cytokine dramatically stimulates differentiation in macrophages primed by less than one percent of the amount of RANKL (ligand for the receptor activator of NF-kappaB) required to induce osteoclast formation. Mirroring their synergistic effects on osteoclast differentiation, TNF-alpha and RANKL markedly potentiate NF-kappaB and stress-activated protein kinase/c-Jun NH(2)-terminal kinase activity, two signaling pathways essential for osteoclastogenesis. In vivo administration of TNF-alpha prompts robust osteoclast formation in chimeric animals in which ss-galactosidase positive, TNF-responsive macrophages develop within a TNF-nonresponsive stromal environment. Thus, while TNF-alpha alone does not induce osteoclastogenesis, it does so both in vitro and in vivo by directly targeting macrophages within a stromal environment that expresses permissive levels of RANKL. Given the minuscule amount of RANKL sufficient to synergize with TNF-alpha to promote osteoclastogenesis, TNF-alpha appears to be a more convenient target in arresting inflammatory osteolysis.

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Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand.
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
RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis, and regulation of bone mass and calcium metabolism.
Li, J., Sarosi, I., Yan, X.-Q., Morony, S., Capparelli, C., Tan, H.-L., McCabe, S., Elliott, R., Scully, S., Van, G., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.4.1566 · Cited by 1,119

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Research works printed but not linked: 26

Lannigan, 1993, J Laryngol Otol, 107, 12, 10.1017/S0022215100122005 · DOI
Baroukh, 1991, J Periodontal Res, 26, 161, 10.1111/j.1600-0765.1991.tb01640.x · DOI
Nair, 1996, Infect Immun, 64, 2371, 10.1128/IAI.64.7.2371-2380.1996 · DOI
Bom-van Noorloos, 1990, J Clin Periodontol, 17, 409, 10.1111/j.1600-051X.1990.tb02338.x · DOI
Birkedal-Hansen, 1993, J Periodontal Res, 28, 500, 10.1111/j.1600-0765.1993.tb02113.x · DOI
Abu-Amer, 1997, J Clin Invest, 100, 1557, 10.1172/JCI119679 · DOI
Abu-Amer, 1998, J Biol Chem, 273, 29417, 10.1074/jbc.273.45.29417 · DOI
Teitelbaum, 2000, Science, 289, 1504, 10.1126/science.289.5484.1504 · DOI · Paper page
Quinn, 2000, J Bone Miner Res, 15, 1459, 10.1359/jbmr.2000.15.8.1459 · DOI
Ross, 2000, J Clin Invest, 105, 555, 10.1172/JCI9557 · DOI
Kobayashi, 2000, J Exp Med, 191, 275, 10.1084/jem.191.2.275 · DOI
Azuma, 2000, J Biol Chem, 275, 4858, 10.1074/jbc.275.7.4858 · DOI · Paper page
McHugh, 2000, J Clin Invest, 105, 433, 10.1172/JCI8905 · DOI
Sudo, 1995, Oncogene, 11, 2469
Beutler, 1987, Lymphokines, 14, 203, 10.1016/B978-0-12-432014-7.50012-7 · DOI
Ledgerwood, 1999, Lab Invest, 79, 1041
Siwik, 2000, Circ Res, 86, 1259, 10.1161/01.RES.86.12.1259 · DOI
Hofbauer, 1999, Bone, 25, 255, 10.1016/S8756-3282(99)00162-3 · DOI
Horwood, 1998, Endocrinology, 139, 4743, 10.1210/endo.139.11.6433 · DOI
Kitazawa, 1994, J Clin Invest, 94, 2397, 10.1172/JCI117606 · DOI
Thomson, 1987, J Immunol, 138, 775, 10.4049/jimmunol.138.3.775 · DOI
Lerner, 1993, J Bone Miner Res, 8, 147, 10.1002/jbmr.5650080205 · DOI
van der Pluijm, 1991, Endocrinology, 129, 1596, 10.1210/endo-129-3-1596 · DOI
Simonet, 1997, Cell, 89, 309, 10.1016/S0092-8674(00)80209-3 · DOI · Paper page
Iotsova, 1997, Nat Med, 11, 1285, 10.1038/nm1197-1285 · DOI
Grigoriadis, 1994, Science, 266, 443, 10.1126/science.7939685 · DOI

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Background
Metabolic activation stimulates acid secretion and expression of matrix degrading proteases in human osteoblasts
George, M., Stein, B., Müller, O., Weis-Klemm, M., Pap, T., Parak, W. J., & Aicher, W. (2003) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2002.005256 · Cited by 23
Osteopenia and osteoporosis in gastrointestinal diseases: Diagnosis and treatment
Southerland, J. C., & Valentine, J. F. (2001) · Current Gastroenterology Reports · doi:10.1007/s11894-001-0082-8 · Cited by 19
Immune-Mediated Muscle Diseases of the Horse
Durward-Akhurst, S., & Valberg, S. (2018) · Veterinary Pathology-Supplement · doi:10.1177/0300985816688755 · Cited by 23
A Systems Approach to Understanding Bone Cell Interactions in Health and Disease
Pivonka, P., Buenzli, P. R., & Dunst, C. R. (2012) · InTech eBooks · doi:10.5772/51149 · Cited by 21
Control of Osteoclast Activity and Bone Loss by IKK Subunits: New Targets for Therapy
Ruocco, M. G., & Karin, M. (2007) · Advances in experimental medicine and biology · doi:10.1007/978-0-387-72009-8_16 · Cited by 18
Immune cells: the key mediator between the gut microbiota and osteoporosis
Ma, T., Zhang, T., Peng, C., Liu, K., Xiong, Y., Chen, K., Peng, N., Wei, Z., Kuang, J., & Ou, L. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1680021 · Cited by 22
Bone involvement in monogenic autoinflammatory syndromes
Bader‐Meunier, B., Nieuwenhove, E. V., Breton, S., & Wouters, C. H. (2017) · Rheumatology · doi:10.1093/rheumatology/kex306 · Cited by 24
The blocking of uPAR suppresses lipopolysaccharide‐induced inflammatory osteoclastogenesis and the resultant bone loss through attenuation of integrin β3/Akt pathway
Kanno, Y., Ishisaki, A., Miyashita, M., & Matsuo, O. (2016) · Immunity, Inflammation and Disease · doi:10.1002/iid3.116 · Cited by 22
“LPS-stimulated osteoclastogenesis is mediated by TNF-a [35, 36].”
The Effect of Class A Scavenger Receptor Deficiency in Bone*
Lin, Y.-L., de Villiers, W. D., Garvy, B., Post, S., Nagy, T., Safadi, F., Faugere, M., Wang, G., Malluche, H., & Williams, J. P. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608552200 · Cited by 22
Targeting APJ drives BNIP3-PINK1-PARKIN induced mitophagy and improves systemic inflammatory bone loss
Wang, W., Wang, Q., Li, W., Xu, H. Y., Liang, X., Wang, W., Li, N., Yang, H., Xu, Y., Bai, J., et al. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.12.033 · Cited by 19
Effects of Metabolic Dysfunction-Associated Steatotic Liver Disease on Bone Density and Fragility Fractures: Associations and Mechanisms
Khanmohammadi, S., & Kuchay, M. S. (2024) · Journal of Obesity & Metabolic Syndrome · doi:10.7570/jomes24004 · Cited by 21
“60,61 T2DM may not affect bone mass but impairs bone quality due to the accumulation of advanced glycation end-products, leading to increasing fracture risk at a relatively higher BMD compared to people without T2DM.”
Background
Macrophages in the process of osseointegration around the implant and their regulatory strategies
Fang, X., Sun, D., Li, Y., Han, X., Gan, Y.-L., Jiao, J., Jiang, M., Gong, H., Qi, Y., & Zhao, J.-H. (2024) · Connective Tissue Research · doi:10.1080/03008207.2023.2300455 · Cited by 21
“In addition, OPG also affects the cytoplasmic expression of cyclin A and CDK2 and thus promotes the proliferation of MSCs 51 .”
Background
Proximity-labeling chemoproteomics defines the subcellular cysteinome and inflammation-responsive mitochondrial redoxome
Yan, T., Julio, A., Villanueva, M., Jones, A. E., Ball, A. B., Boatner, L. M., Turmon, A. C., Yen, S. L., Desai, H., Divakaruni, A. S., et al. (2023) · bioRxiv · doi:10.1101/2023.01.22.525042 · Cited by 21
Salvianolate Ameliorates Osteopenia and Improves Bone Quality in Prednisone-Treated Rheumatoid Arthritis Rats by Regulating RANKL/RANK/OPG Signaling
Gao, X., Wu, Q., Zhang, X.-L., Tian, J., Liang, D., Min, Y., Lu, J., Zhang, X.-M., Cui, L., Xu, B.-L., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.710169 · Cited by 21
Myeloid Krüppel-Like Factor 2 Critically Regulates K/BxN Serum-Induced Arthritis
Das, M., Deb, M., Laha, D., Joseph, M., Kanji, S., Aggarwal, R., Iwenofu, O. H., Pompili, V. J., Jarjour, W. N., & Das, H. (2019) · Cells · doi:10.3390/cells8080908 · Cited by 21
“RANKL could be substituted by TNF-α, which also mediates osteoclast formation from mouse bone marrow cells [55,56].”
Background
Lamins and bone disorders: current understanding and perspectives
Gargiuli, C., Schena, E., Mattioli, E., Columbaro, M., D’Apice, M. R., Novelli, G., Greggi, T., & Lattanzi, G. (2018) · Oncotarget · doi:10.18632/oncotarget.25071 · Cited by 25
Splenomegaly, myeloid lineage expansion and increased osteoclastogenesis in osteogenesis imperfecta murine
Matthews, B., Roeder, E., Wang, X., Aguila, H., Lee, S.-K., Grčević, D., & Kalajzić, I. (2017) · Bone · doi:10.1016/j.bone.2017.06.004 · Cited by 21
“However, it is well established that inflammatory cytokines such as TNFα can act synergistically with RANKL to stimulate increased osteoclastogenesis [5].”
Background
An update on the use of tumor necrosis factor alpha inhibitors in the treatment of ankylosing spondylitis
Osman, M., & Maksymowych, W. (2017) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2016.1218761 · Cited by 21
“with TNFα alone, increased osteoclast formation in vitro [11].”
Background
CCAAT/Enhancer-binding Protein α (C/EBPα) Is Important for Osteoclast Differentiation and Activity
Jules, J., Chen, W., Feng, X., & Li, Y. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.674598 · Cited by 20
STAMPing at the crossroads of normal physiology and disease states
Sikkeland, J., Sheng, X., Jin, Y., & Saatcioglu, F. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.02.013 · Cited by 29
p38 MAPK as a Potential Therapeutic Target for Inflammatory Osteolysis
Shi, W., & Siegal, G. P. (2006) · Advances in Anatomic Pathology · doi:10.1097/pap.0b013e31802ef4f2 · Cited by 19
“As the magnitude of inflammation and TNF-a production increases, substantial osteoclastogenesis is achieved by direct targeting of the cytokine to the osteoclast precursors even in the absence of TNF-a–responsive stromal cells.(1,30) IL-1 mediates a substantial portion, but not all, of TNF-a–induced osteoclast recruit…”
Background
A Rapid Multiparameter Approach to Study Factors that Regulate Osteoclastogenesis: Demonstration of the Combinatorial Dominant Effects of TNF-α and TGF-ß in RANKL-Mediated Osteoclastogenesis
Huang, W., Drissi, M., O'Keefe, R. J., & Schwarz, E. M. (2003) · Calcified Tissue International · doi:10.1007/s00223-003-0059-8 · Cited by 21
“Our data are consistent with the hypothesis that TNF-a-induced osteoclastogenesis requires ‘‘permissive’’ low-levels of RANKL [7].”
Influential
Cornus officinalis: a potential herb for treatment of osteoporosis
Tang, X., Huang, Y., Fang, X., Tong, X., Qian, Y., Zheng, W., & Fu, F. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1289144 · Cited by 17
“Besides, the upregulation of TNF-α expression in T-lymphocytes, under the regulation of RANKL, promotes the apoptosis of OB (60, 64).”
Background
Neutralization of Staphylococcus aureus Protein A Prevents Exacerbated Osteoclast Activity and Bone Loss during Osteomyelitis
Gehrke, A.-K. E., Bertelli, A. M., Ledo, C., Gonzalez, C. D., Llana, M. N., Blanco, C., Sordelli, D. O., Putman, N. E., Cassat, J. E., Delpino, M. V., et al. (2022) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01140-22 · Cited by 19
“promoting the differentiation of osteoclasts (28) and at the same time inhibiting osteoblast”
Background
Gasdermin D deficiency attenuates arthritis induced by traumatic injury but not autoantibody-assembled immune complexes
Yang, T., Sun, K., Wang, C., Swarnkar, G., Quan, S., Kress, D., Xiao, J., Alippe, Y., Zheng, H., Brophy, R. H., et al. (2021) · Arthritis Research & Therapy · doi:10.1186/s13075-021-02668-8 · Cited by 22
TNF-Polarized Macrophages Produce Insulin-like 6 Peptide to Stimulate Bone Formation in Rheumatoid Arthritis in Mice
Yi, X., Liu, X., Kenney, H. M., Duan, R., Lin, X., Schwarz, E. M., & Yao, Z. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4447 · Cited by 23
“TNFα induces osteoclastogenesis not only indirectly by stimulating RANKL production by accessory cells((43)) but also directly by sequentially activating NF-κB, c-Fos followed by NFATc1, similar to and independent of RANKL;((18,44)) it can also regulate bone formation both negatively and positively by activating NF-κB…”
Background
Fc-gamma receptors and S100A8/A9 cause bone erosion during rheumatoid arthritis. Do they act as partners in crime?
Ceglie, I. D., Kruisbergen, N., van den Bosch, M. V. D., & van Lent, P. V. (2019) · Rheumatology · doi:10.1093/rheumatology/kez218 · Cited by 20
The Uncovered Role of Immune Cells and NK Cells in the Regulation of Bone Metastasis
Roato, I., & Vitale, M. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00145 · Cited by 18
PDGF is a potent initiator of bone formation in a tissue engineered model of pathological ossification
Davies, O., Grover, L., Lewis, M., & Liu, Y. (2017) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2320 · Cited by 20
“…factorial design: IL1β (0.02 ng/ml; Barksby et al., 2006), IL6 (10 ng/ml; Nasi et al., 2015), PDGF-BB (2 ng/ml; Zhao et al., 2016), TNFα (1 ng/ml; Lam et al., 2000), TGFβ (1 ng/ml; Pfeilschifter et al., 1990), BMP2 (300 ng/ml; Katagiri et al., 1994), basic fibroblast growth factor (bFGF) (1…”
Influential
Pasteurella multocida Toxin Triggers RANKL-Independent Osteoclastogenesis
Chakraborty, S., Kloos, B., Harre, U., Schett, G., & Kubatzky, K. F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00185 · Cited by 20
“TNF-α alone is a weak inducer of osteoclastogenesis in mouse BMDM (43), but has been reported to induce functional osteoclast formation along with IL-6 (44) or IL-1 (45).”
Background
Effects of the stem extracts of Schisandra glaucescens Diels on collagen-induced arthritis in Balb/c mice.
Xiang, Y., Zhang, T.-T., Yin, C.-P., Zhou, J.-W., Huang, R., Gao, S.-S., Zheng, L., Wang, X.-G., Manyande, A., Tian, X.-B., et al. (2016) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2016.11.011 · Cited by 20
Activation status of γδ T cells dictates their effect on osteoclast generation and bone resorption
Phalke, S., & Chiplunkar, S. V. (2015) · Bone Reports · doi:10.1016/j.bonr.2015.10.004 · Cited by 24
“The data indicates that other cytokines like TNFα and IL17 may also contribute to the pro-osteoclastogenic effect, which may be present in the supernatants after blocking IL6 (Supplementary Table 1).”
BackgroundInfluential
The antibody atliximab attenuates collagen-induced arthritis by neutralizing AIMP1, an inflammatory cytokine that enhances osteoclastogenesis
Hong, S. H., Cho, J. G., Yoon, K. J., Lim, D., Kim, C. H., Lee, S., & Park, S. G. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2014.12.017 · Cited by 18
Characterization and Identification of Subpopulations of Mononuclear Preosteoclasts Induced by TNF-α in Combination with TGF-β in Rats
Matsubara, R., Kukita, T., Ichigi, Y., Takigawa, I., Qu, P. F., Funakubo, N., Miyamoto, H., Nonaka, K., & Kukita, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047930 · Cited by 24
“Previous studies have shown that TNF-a induced osteoclast formation from RANKL-primed or TGF-b-primed mouse BMM in a RANKL-RANK independent manner in vitro [24,25].”
Background
HDAC inhibitor, trichostatin A suppresses osteoclastogenesis by up-regulating the expression of C/EBP-β and MKP-1
Williams, P., Nishu, K., & Rahman, M. M. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06286.x · Cited by 20
The tumor necrosis factor type 2 receptor plays a protective role in tumor necrosis factor-α-induced bone resorption lacunae on mouse calvariae
Nagano, K., Alles, N., Mian, A. H., Shimoda, A., Morimoto, N., Tamura, Y., Shimokawa, H., Akiyoshi, K., Ohya, K., & Aoki, K. (2011) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-011-0270-z · Cited by 20
Prevention of postmenopausal osteoporosis and associated fractures: Clinical evaluation of the choice between estrogen and bisphosphonates
al-Azzawi, F. (2008) · Gynecological Endocrinology · doi:10.1080/09513590802296245 · Cited by 20
“TNF directly stimulates the formation of osteoclasts precursors, acts synergistically with the levels of NFkB and activator protein-1 (AP-1) signaling to increases RANL activity and synergistically with RANKL to increase the expression of RANK on osteoclasts [16].”
Background
A tumor necrosis factor-alpha antagonist inhibits inflammatory bone resorption induced by Porphyromonas gingivalis infection in mice.
Suzuki, Y., Aoki, K., Saito, H., Umeda, M., Nitta, H., Baron, R., & Ohya, K. (2006) · Journal of Periodontal Research · doi:10.1111/j.1600-0765.2005.00812.x · Cited by 20
Cytokines and fracture healing
Cho, T., Gerstenfeld, L., Barnes, G., & Einhorn, T. (2001) · Current Opinion in Orthopedics · doi:10.1097/00001433-200110000-00007 · Cited by 20
Immunology of Gut-Bone Signaling
Collins, F. L., Schepper, J. D., Rios‐Arce, N. D., Steury, M. D., Kang, H. J., Mallin, H., Schoenherr, D. T., Camfield, G., Chishti, S., McCabe, L. R., et al. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-66653-2_5 · Cited by 22
Lysophosphatidic acid stimulates osteoclast fusion through OC-STAMP and P2X7 receptor signaling
Hwang, Y., Ma, G.-T., Park, K.-K., & Chung, W.-Y. (2013) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-013-0470-9 · Cited by 20

Authors: Lam, J., Takeshita, S., Barker, J. E., Kanagawa, O., Ross, F. P., & Teitelbaum, S. L.
Affiliations: Washington University in St. Louis (US)
Barnes-Jewish Hospital (US)
Corresponding author: Teitelbaum, Steven L.
ORCID: Kanagawa, Osami
Teitelbaum, Steven L.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2000-12-15
Volume: 106
Issue: 12
Pages: 1481-1488
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci11176
PMC: PMC387259
OpenAlex: W2132933661
Cited by: 1,440
References: 0
Citations by year: 2026: 45 · 2025: 63 · 2024: 48 · 2023: 53 · 2022: 60 · 2021: 72 · 2020: 57 · 2019: 61 · 2018: 59 · 2017: 75 · 2016: 61 · 2015: 56 · 2014: 49 · 2013: 64 · 2012: 58
FWCI: 11.22
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
Funders: National Institutes of Health
National Institute of General Medical Sciences (T32GM007200)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK027726)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-32788, AR-07033, R01AR032788, R37AR046523, T32AR007033, R01AR046852, AR46523, R01AR046523)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Keywords: TNF-α, osteoclastogenesis, RANK ligand, macrophages, osteoclast precursors, NF-κB signaling, JNK signaling, inflammatory osteolysis, bone destruction, chimeric mice, cytokine synergy
MeSH terms: Animals, Carrier Proteins, Cell Differentiation, Cells, Cultured, Drug Synergism, Enzyme Activation, Flow Cytometry, Histocytochemistry, Macrophages, Membrane Glycoproteins, Osteoclasts, Stem Cells, Tumor Necrosis Factor-alpha, Bone Marrow Transplantation, NF-kappa B, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases, Mice, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B

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TNF-α induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand

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