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Article

Cytokine Inhibitors Upregulate Extracellular Matrix Anabolism of Human Intervertebral Discs under Alginate Beads and Alginate-Embedded Explant Cultures

by
Kenichiro Kakutani
1,2,*,
Takashi Yurube
1,
Howard S. An
2,
Minoru Doita
3 and
Koichi Masuda
4
1
Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
2
Department of Orthopaedic Surgery, Rush University Medical Center, Orthopaedic Building, Suite 300, 1611 W Harrison Street, Chicago, IL 60612, USA
3
Department of Orthopedic Surgery, Iwate Medical University School of Medicine, 2-1-1, Idaidori, Yahaba-cho, Showa-gun, Iwate 028-3895, Japan
4
Department of Orthopaedic Surgery, University of California, San Diego, 9500 Gilman Dr. Mail Code 0863, La Jolla, CA 92093-0863, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(15), 12336; https://doi.org/10.3390/ijms241512336
Submission received: 12 June 2023 / Revised: 26 July 2023 / Accepted: 27 July 2023 / Published: 2 August 2023
(This article belongs to the Special Issue Regeneration for Spinal Diseases 3.0)
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Abstract

We investigated the effects of the cytokine inhibitors IL-1 receptor antagonist (IL-1Ra) and soluble tumor necrosis factor receptor-1 (sTNFR1) on the extracellular matrix metabolism of human intervertebral discs (IVDs) and the roles of IL-1β and TNF in the homeostasis of IVD cells. The 1.2% alginate beads and the explants obtained from 35 human lumbar discs were treated with cytokine inhibitors. Extracellular matrix metabolism was evaluated by proteoglycan (PG) and collagen syntheses and IL-1β, TNF, and IL-6 expressions after three days of culture in the presence or absence of IL-1Ra, sTNFR1, and cycloheximide. Simultaneous treatment with IL-1Ra and sTNFR1 stimulated PG and collagen syntheses in the NP and AF cells and explants. The IL-1β concentration was significantly correlated to the relative increase in PG synthesis in AF explants after simultaneous cytokine inhibitor treatment. The relative increase in PG synthesis induced by simultaneous cytokine treatment was significantly higher in an advanced grade of MRI. Expressions of IL-1β and TNF were upregulated by each cytokine inhibitor, and simultaneous treatment suppressed IL-1β and TNF productions. In conclusion, IL-1Ra and sTNFR1 have the potential to increase PG and collagen synthesis in IVDs. IL-1β and TNF have a feedback pathway to maintain optimal expression, resulting in the control of homeostasis in IVD explants.
Keywords: cytokine; intervertebral disc metabolism; autocrine cytokine; intervertebral disc metabolism; autocrine

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MDPI and ACS Style

Kakutani, K.; Yurube, T.; An, H.S.; Doita, M.; Masuda, K. Cytokine Inhibitors Upregulate Extracellular Matrix Anabolism of Human Intervertebral Discs under Alginate Beads and Alginate-Embedded Explant Cultures. Int. J. Mol. Sci. 2023, 24, 12336. https://doi.org/10.3390/ijms241512336

AMA Style

Kakutani K, Yurube T, An HS, Doita M, Masuda K. Cytokine Inhibitors Upregulate Extracellular Matrix Anabolism of Human Intervertebral Discs under Alginate Beads and Alginate-Embedded Explant Cultures. International Journal of Molecular Sciences. 2023; 24(15):12336. https://doi.org/10.3390/ijms241512336

Chicago/Turabian Style

Kakutani, Kenichiro, Takashi Yurube, Howard S. An, Minoru Doita, and Koichi Masuda. 2023. "Cytokine Inhibitors Upregulate Extracellular Matrix Anabolism of Human Intervertebral Discs under Alginate Beads and Alginate-Embedded Explant Cultures" International Journal of Molecular Sciences 24, no. 15: 12336. https://doi.org/10.3390/ijms241512336

APA Style

Kakutani, K., Yurube, T., An, H. S., Doita, M., & Masuda, K. (2023). Cytokine Inhibitors Upregulate Extracellular Matrix Anabolism of Human Intervertebral Discs under Alginate Beads and Alginate-Embedded Explant Cultures. International Journal of Molecular Sciences, 24(15), 12336. https://doi.org/10.3390/ijms241512336

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