The DOI matches its Crossref record; 54 of the 55 references it cites were found in a registry or an index.
Interleukin-4 Reversibly Inhibits Osteoclastogenesis via Inhibition of NF-κB and Mitogen-activated Protein Kinase Signaling
Open accessAbstract
To define the molecular mechanism(s) by which interleukin (IL)-4 reversibly inhibits formation of osteoclasts (OCs) from bone marrow macrophages (BMMs), we examined the capacity of this T cell-derived cytokine to impact signals known to modulate osteoclastogenesis, which include those initiated by macrophage colony-stimulating factor (M-CSF), receptor for activation of NF-kappa B ligand (RANKL), tumor necrosis factor (TNF), and IL-1. We find that although pretreatment of BMMs with IL-4 does not alter M-CSF signaling, it reversibly blocks RANKL-dependent activation of the NF-kappa B, JNK, p38, and ERK signals. IL-4 also selectively inhibits TNF signaling, while enhancing that of IL-1. Contrary to previous reports, we find that MEK inhibitors dose-dependently inhibit OC differentiation. To identify more proximal signals mediating inhibition of OC formation by IL-4, we used mice lacking STAT6 or SHIP1, two adapter proteins that bind the IL-4 receptor. IL-4 fails to inhibit RANKL/M-CSF-induced osteoclastogenesis by BMMs derived from STAT6-, but not SHIP1-, knockout mice. Consistent with this observation, the inhibitory effects of IL-4 on RANKL-induced NF-kappa B and mitogen-activated protein kinase activation are STAT6-dependent. We conclude that IL-4 reversibly arrests osteoclastogenesis in a STAT6-dependent manner by 1) preventing I kappa B phosphorylation and thus NF-kappa B activation, and 2) blockade of the JNK, p38, and ERK mitogen-activated protein kinase pathways.
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“Wei and associates found that IL-4 inhibited osteoclastogenesis by blocking the JNK, p38, and ERK protein kinase pathways, which are upstream of NFATc1 [40].”
From Osteoclasts and Microgravity (2020) · cites this paper as [40]
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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
Osteoprotegerin: 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
Phosphorylation meets ubiquitination: the control of NF-κB activity
Karin, M., & Ben-Neriah, Y. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.621 · Cited by 4,766
Yasuda, 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
Self-citationA 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
The IL-4 receptor: signaling mechanisms and biologic functions
Nelms, K., Keegan, A. D., Zamorano, J., Ryan, J. J., & Paul, W. E. (1999) · Annual Review of Immunology · doi:10.1146/annurev.immunol.17.1.701 · Cited by 1,545
Lam, J., Takeshita, S., Barker, J. E., Kanagawa, O., Ross, F. P., & Teitelbaum, S. L. (2000) · Journal of Clinical Investigation · doi:10.1172/jci11176 · Cited by 1,440
Self-citationKobayashi, K., Takahashi, N., Jimi, E., Udagawa, N., Takami, M., Kotake, S., Nakagawa, N., Kinosaki, M., Yamaguchi, K., Shima, N., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.2.275 · Cited by 1,309
TRAF6 is a signal transducer for interleukin-1
Cao, Z., Xiong, J., Takeuchi, M., Kurama, T., & Goeddel, D. V. (1996) · Nature · doi:10.1038/383443a0 · Cited by 1,305
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Items 201–202 of 202
Danzeng, Q., Wu, F., Cui, M., Shen, Y., Li, Y., Jiao, J., & Jiang, W. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1826988 · Cited by 2
Targeted IL-4 nanoparticles for osteal macrophages modulation in osteoporosis
Martínez-Borrajo, R., Beule, P. D., Alcoba-Pacheco, A., Landín, M., & Díaz‐Rodríguez, P. (2026) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2026.107542
Metadata
- Authors
- Wei, S., Wang, M. W.-H., Teitelbaum, S. L., & Ross, F. P.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Ross, F. Patrick
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-02
- Volume
- 277
- Issue
- 8
- Pages
- 6622-6630
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1998128158
- Cited by
- 202
- References
- 55
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 4 · 2021: 3 · 2020: 15 · 2019: 3 · 2018: 9 · 2017: 5 · 2016: 7 · 2015: 6 · 2014: 3 · 2013: 10 · 2012: 5
- FWCI
- 5.55
- 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
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- IL-4, osteoclastogenesis, NF-κB signaling, mitogen-activated protein kinase, STAT6, SHIP1, RANKL, macrophage colony-stimulating factor, TNF signaling, IL-1 signaling, MEK inhibitors, bone marrow-derived macrophages
- MeSH terms
- Animals, Bone Marrow Cells, Carrier Proteins, Cells, Cultured, Gene Expression Regulation, Kinetics, Macrophages, Membrane Glycoproteins, Mice, Inbred C57BL, Osteoclasts, Osteogenesis, Signal Transduction, Interleukin-4, Macrophage Colony-Stimulating Factor, NF-kappa B, Cell Culture Techniques, Reverse Transcriptase Polymerase Chain Reaction, MAP Kinase Signaling System, Mice, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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