The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
TNF-α and IL-1β Promote a Disintegrin-like and Metalloprotease with Thrombospondin Type I Motif-5-mediated Aggrecan Degradation through Syndecan-4 in Intervertebral Disc
Open accessAbstract
Elevated levels of TNF-α, IL-1β and a resultant increase in ADAMTS (a disintegrin-like and metalloprotease with thrombospondin type I motifs) expression is seen during disc degeneration. However, if these pro-inflammatory cytokines control ADAMTS activity is not definitively known. The goal of the investigation was to study if TNF-α and IL-1β regulate syndecan-4 (SDC4) expression, and if SDC4 was responsible for promoting aggrecan degradation through controlling ADAMTS activity in nucleus pulposus cells of the intervertebral disc. Cytokine treatment increased SDC4 expression and promoter activity. Use of inhibitor, SM7368 and co-transfections with IκBα, RelA/p50 showed that NF-κΒ regulated both basal and cytokine-dependent SDC4 transcription. SDC4 promoter harboring RelA binding site mutation was unresponsive to the cytokines. Moreover, cytokines failed to increase SDC4 promoter activity in RelA-null cells. Cytokines increased ADAMTS-4/5 expression and aggrecan degradation and promoted SDC4 interaction with ADAMTS-5. Treatment with heparinase-III and p-nitrophenyl-β-D-xylopyranoside (PNPX), an inhibitor of heparan sulfate synthesis and transfection with SDC4-shRNA partially blocked cytokine mediated aggrecan degradation. Analysis of human tissues showed increased aggrecan degradation with a concomitant increase in SDC4 and ADAMTS-5 protein expression with severity of disc disease. Likewise, SDC4, TNF-α, IL-1β, ADAMTS-4, and ADAMTS-5 mRNA expression increased in degenerate tissues. We conclude that in nucleus pulposus, TNF-α and IL-1β regulate SDC4 expression, which plays a key role in pathogenesis of degenerative disc disease by promoting aggrecan degradation by ADAMTS-5.
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Cites
Magnetic Resonance Classification of Lumbar Intervertebral Disc Degeneration
Pfirrmann, C. W. A., Metzdorf, A., Zanetti, M., Hodler, J., & Boos, N. (2001) · Spine · doi:10.1097/00007632-200109010-00011 · Cited by 4,012
Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis
Glasson, S. S., Askew, R., Sheppard, B., Carito, B., Blanchet, T., Ma, H.-L., Flannery, C. R., Peluso, D., Kanki, K., Yang, Z., et al. (2005) · Nature · doi:10.1038/nature03369 · Cited by 1,253
ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro
Stanton, H., Rogerson, F. M., East, C. J., Golub, S. B., Lawlor, K. E., Meeker, C. T., Little, C. B., Last, K., Farmer, P. J., Campbell, I. K., et al. (2005) · Nature · doi:10.1038/nature03417 · Cited by 915
HISTOLOGY AND PATHOLOGY OF THE HUMAN INTERVERTEBRAL DISC
ROBERTS, S., EVANS, H., TRIVEDI, J., & MENAGE, J. (2006) · The Journal of Bone and Joint Surgery-American Volume · doi:10.2106/00004623-200604002-00003 · Cited by 828
The role of interleukin-1 in the pathogenesis of human Intervertebral disc degeneration
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Le Maitre, C. L., Hoyland, J. A., & Freemont, A. J. (2007) · Arthritis Research & Therapy · doi:10.1186/ar2275 · Cited by 580
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Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis
Echtermeyer, F., Bertrand, J., Dreier, R., Meinecke, I., Neugebauer, K., Fuerst, M., Lee, Y. J., Song, Y. W., Herzog, C., Theilmeier, G., et al. (2009) · Nature Medicine · doi:10.1038/nm.1998 · Cited by 318
Cited by
Role of cytokines in intervertebral disc degeneration: pain and disc content
Risbud, M. V., & Shapiro, I. M. (2014) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2013.160 · Cited by 1,767
Self-citationLyu, F.-J., Cui, H., Pan, H., MC Cheung, K., Cao, X., Iatridis, J. C., & Zheng, Z. (2021) · Bone Research · doi:10.1038/s41413-020-00125-x · Cited by 474
Self-citationDisc in flames: Roles of TNF-α and IL-1β in intervertebral disc degeneration
1025 Walnut Street, S. 5. C. B., Johnson, Z., Schoepflin, Z., Choi, H., Shapiro, I., & Risbud, M. (2015) · European Cells and Materials · doi:10.22203/ecm.v030a08 · Cited by 386
Self-citationMohd Isa, I. L., Teoh, S. L., Mohd Nor, N. H., & Mokhtar, S. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010208 · Cited by 365
Cheng, X., Zhang, L., Zhang, K., Zhang, G., Hu, Y., Sun, X., Zhao, C., Li, H., Li, Y. M., & Zhao, J. (2018) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2017-212056 · Cited by 280
Metadata
- Authors
- Wang, J., Markova, D., Anderson, D. G., Zheng, Z., Shapiro, I. M., & Risbud, M. V.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 286
- Issue
- 46
- Pages
- 39738-39749
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1979264581
- Cited by
- 270
- References
- 25
- FWCI
- 9.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: TNF-α and IL-1β Promote a Disintegrin-like and Metalloprotease with Thrombospondin Type I Motif-5-mediated Aggrecan Degradation through Syndecan-4 in Intervertebral Disc. https://app.cochat.ai/papers/10.1074/jbc.m111.264549
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- Wang, J., Markova, D., Anderson, D. G., Zheng, Z., Shapiro, I. M., & Risbud, M. V. (2011). TNF-α and IL-1β Promote a Disintegrin-like and Metalloprotease with Thrombospondin Type I Motif-5-mediated Aggrecan Degradation through Syndecan-4 in Intervertebral Disc. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m111.264549
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