Tumor Necrosis Factor-α Induces Differentiation of and Bone Resorption by Osteoclasts
Open accessAbstract
Osteoclast progenitors differentiate into mature osteoclasts in the presence of receptor activator of NF-kappaB (RANK) ligand on stromal or osteoblastic cells and monocyte macrophage colony-stimulating factor (M-CSF). The soluble RANK ligand induces the same differentiation in vitro without stromal cells. Tumor necrosis factor-alpha (TNF-alpha), a potent cytokine involved in the regulation of osteoclast activity, promotes bone resorption via a primary effect on osteoblasts; however, it remains unclear whether TNF-alpha can also directly induce the differentiation of osteoclast progenitors into mature osteoclasts. This study revealed that TNF-alpha directly induced the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs), which produced resorption pits on bone in vitro in the presence of M-CSF. The bone resorption activity of TNF-alpha-induced MNCs was lower than that of soluble RANK ligand-induced MNCs; however, interleukin-1beta stimulated this activity of TNF-alpha-induced MNCs without an increase in the number of MNCs. In this case, interleukin-1beta did not induce TRAP-positive MNC formation. The osteoclast progenitors expressed TNF receptors, p55 and p75; and the induction of TRAP-positive MNCs by TNF-alpha was inhibited completely by an anti-p55 antibody and partially by an anti-p75 antibody. Our findings presented here are the first to indicate that TNF-alpha is a crucial differentiation factor for osteoclasts. Our results sugges…
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TNF-α induces osteoclastogenesis in RANKL- and M-CSF-positive hematopoietic cell precursors, with effects mediated by TNF-α receptors type 1 and type 2, the former being most effective in inducing differentiation of TRAP-positive multinucleated cells.
“TNF-α induces osteoclastogenesis in RANKL- and M-CSF-positive hematopoietic cell precursors [29,30], where its effects are mediated by TNF-α receptors type 1 (p55r) and type 2 (p75r), the former being the most effective in inducing the differentiation of TRAP-positive multinucleated cells [31].”
From Osteoclasts and Microgravity (2020) · cites this paper as [31]
IL-1β enhances the ability of TNF-α to upregulate bone resorption by TRAP-positive multinucleated cells.
“Azuma and associates found that IL-1β enhanced the ability of TNF-α to upregulate bone resorption by TRAP-positive multinucleated cells [31].”
From Osteoclasts and Microgravity (2020) · cites this paper as [31]
Cites
The interleukin‐1 family: 10 years of discovery <sup>1</sup>
Dinarello, C. A. (1994) · The FASEB Journal · doi:10.1096/fasebj.8.15.8001745 · Cited by 783 · see citing works
Flagged first, then by citations
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Feng, X., & McDonald, J. M. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130203 · Cited by 1,272 · see citing works
Kearns, A. E., Khosla, S., & Kostenuik, P. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0014 · Cited by 824 · see citing works
Role of receptor activator of nuclear factor-κB ligand and osteoprotegerin in bone cell biology
Hofbauer, L. C., & Heufelder, A. E. (2001) · Journal of Molecular Medicine · doi:10.1007/s001090100226 · Cited by 586 · see citing works
Regulation of Osteoclast Differentiation by Cytokine Networks
Amarasekara, D. S., Yun, H., Kim, S., Lee, N., Kim, H., & Rho, J. (2018) · Immune Network · doi:10.4110/in.2018.18.e8 · Cited by 518 · see citing works
Roggia, C., Gao, Y., Cenci, S., Weitzmann, M. N., Toraldo, G., Isaia, G., & Pacifici, R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251534698 · Cited by 513 · see citing works
Osteoclasts are essential for TNF-α-mediated joint destruction.
Redlich, K., Hayer, S., Ricci, R., David, J.-P., Tohidast-Akrad, M., Kollias, G., Steiner, G., Smolen, J. S., Wagner, E. F., & Schett, G. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215582 · Cited by 474 · see citing works
Redlich, K., Hayer, S., Maier, A., Dunstan, C. R., Tohidast‐Akrad, M., Lang, S., Türk, B., Pietschmann, P., Woloszczuk, W., Haralambous, S., et al. (2002) · Arthritis & Rheumatism · doi:10.1002/art.10097 · Cited by 285 · see citing works
Li, P., Schwarz, E. M., O'Keefe, R. J., Ma, L., Boyce, B. F., & Xing, L. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.0301233 · Cited by 220 · see citing works
Wei, S., Wang, M. W.-H., Teitelbaum, S. L., & Ross, F. P. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m104957200 · Cited by 202 · see citing works
Osteoclasts are important for bone angiogenesis
Cackowski, F. C., Anderson, J. L., Patrene, K. D., Choksi, R. J., Shapiro, S. D., Windle, J. J., Blair, H. C., & Roodman, G. D. (2010) · Blood · doi:10.1182/blood-2009-08-237628 · Cited by 188 · see citing works
Zhao, B., Grimes, S. N., Li, S., Hu, X., & Ivashkiv, L. B. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20111566 · Cited by 182 · see citing works
Pettit, A. R., Walsh, N. C., Manning, C., Goldring, S. R., & Gravallese, E. M. (2006) · Rheumatology · doi:10.1093/rheumatology/kel045 · Cited by 151 · see citing works
Osteoprotegerin protects against generalized bone loss in tumor necrosis factor-transgenic mice.
Schett, G., Redlich, K., Hayer, S., Zwerina, J., Bolon, B., Dunstan, C., Görtz, B., Schulz, A., Bergmeister, H., Kollias, G., et al. (2003) · Arthritis & Rheumatism · doi:10.1002/art.11150 · Cited by 150 · see citing works
Redlich, K., Görtz, B., Hayer, S., Zwerina, J., Doerr, N., Kostenuik, P., Bergmeister, H., Kollias, G., Steiner, G., Smolen, J. S., et al. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63144-6 · Cited by 134 · see citing works
O' Gradaigh, D., Ireland, D., Bord, S., & Compston, J. E. (2004) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2003.008458 · Cited by 111 · see citing works
The role of interferon-gamma in hematopoietic stem cell development, homeostasis, and disease
Morales-Mantilla, D. E., & King, K. Y. (2018) · Current Stem Cell Reports · doi:10.1007/s40778-018-0139-3 · Cited by 99 · see citing works
Cheng, X., Kinosaki, M., Takami, M., Choi, Y., Zhang, H., & Murali, R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309690200 · Cited by 92 · see citing works
(Pre-)Osteoclasts Induce Retraction of Osteoblasts Before Their Fusion to Osteoclasts
Perez-Amodio, S., Beertsen, W., & Everts, V (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.040509 · Cited by 70 · see citing works
Smith, J. K. (2020) · Life · doi:10.3390/life10090207 · Cited by 52 · see citing works
Shen, W.-R., Kimura, K., Ishida, M., Sugisawa, H., Kishikawa, A., Shima, K., Ogawa, S., Qi, J., & Kitaura, H. (2018) · Journal of Immunology Research · doi:10.1155/2018/5783639 · Cited by 45 · see citing works
Zhu, S., He, H., Gao, C., Luo, G., Xie, Y., Wang, H., Tian, L., Chen, X., Yu, X., & He, C. (2018) · Journal of Molecular Endocrinology · doi:10.1530/jme-17-0218 · Cited by 44 · see citing works
DPP-4 inhibitor impedes lipopolysaccharide-induced osteoclast formation and bone resorption in vivo
Ishida, M., Shen, W.-R., Kimura, K., Kishikawa, A., Shima, K., Ogawa, S., Qi, J., Ohori, F., Noguchi, T., Marahleh, A., et al. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.10.052 · Cited by 36 · see citing works
A novel modified RANKL variant can prevent osteoporosis by acting as a vaccine and an inhibitor
Ko, Y. J., Sohn, H. M., Jang, Y., Park, M., Kim, B., Kim, B., Park, J., Hyun, H., Jeong, B., Hong, C., et al. (2021) · Clinical and Translational Medicine · doi:10.1002/ctm2.368 · Cited by 23 · see citing works
- Authors
- Azuma, Y., Kaji, K., Katogi, R., Takeshita, S., & Kudo, A.
- Affiliations
- Teijin (Japan) (JP)
- Tokyo Institute of Technology (JP)
- ORCID
- Azuma, Yoshiaki
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-02
- Volume
- 275
- Issue
- 7
- Pages
- 4858-4864
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2019146941
- Cited by
- 731
- References
- 1
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 17 · 2023: 23 · 2022: 23 · 2021: 46 · 2020: 50 · 2019: 37 · 2018: 29 · 2017: 22 · 2016: 24 · 2015: 29 · 2014: 24 · 2013: 33 · 2012: 20
- FWCI
- 10.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
- Keywords
- TNF-α, osteoclastogenesis, bone resorption, RANK ligand, macrophage colony-stimulating factor, tartrate-resistant acid phosphatase, multinucleated cells, TNF receptor p55, TNF receptor 2, IL-1β, osteolysis, chronic inflammatory diseases
- MeSH terms
- Animals, Bone Marrow Cells, Bone Resorption, Cell Differentiation, Male, Osteoclasts, Tumor Necrosis Factor-alpha, Antigens, CD, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Mice
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