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Cytokine Inhibitors Upregulate Extracellular Matrix Anabolism of Human Intervertebral Discs under Alginate Beads and Alginate-Embedded Explant Cultures. 2023

Kenichiro Kakutani, and Takashi Yurube, and Howard S An, and Minoru Doita, and Koichi Masuda
Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

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.

UI MeSH Term Description Entries
D007403 Intervertebral Disc Any of the 23 plates of fibrocartilage found between the bodies of adjacent VERTEBRAE. Disk, Intervertebral,Intervertebral Disk,Disc, Intervertebral,Discs, Intervertebral,Disks, Intervertebral,Intervertebral Discs,Intervertebral Disks
D011509 Proteoglycans Glycoproteins which have a very high polysaccharide content. Proteoglycan,Proteoglycan Type H
D003094 Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH). Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen
D005109 Extracellular Matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Matrix, Extracellular,Extracellular Matrices,Matrices, Extracellular
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D017472 Receptors, Interleukin-1 Cell surface receptors that are specific for INTERLEUKIN-1. Included under this heading are signaling receptors, non-signaling receptors and accessory proteins required for receptor signaling. Signaling from interleukin-1 receptors occurs via interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88. IL-1 Receptor,IL-1 Receptors,IL1 Receptor,Interleukin-1 Receptor,Interleukin-1 Receptors,Receptor, Interleukin-1,Receptors, IL-1,IL1 Receptors,Interleukin 1 Receptor,IL 1 Receptor,IL 1 Receptors,Interleukin 1 Receptors,Receptor, IL-1,Receptor, IL1,Receptor, Interleukin 1,Receptors, IL 1,Receptors, IL1,Receptors, Interleukin 1
D053590 Interleukin 1 Receptor Antagonist Protein A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA. Anakinra,Antril,IL-1 Inhibitor, Urine,IL-1Ra,IL1 Febrile Inhibitor,Interleukin 1 Inhibitor, Urine,Kineret,Urine-Derived IL1 Inhibitor,Febrile Inhibitor, IL1,IL 1 Inhibitor, Urine,IL1 Inhibitor, Urine-Derived,Urine Derived IL1 Inhibitor,Urine IL-1 Inhibitor
D055959 Intervertebral Disc Degeneration Degenerative changes in the INTERVERTEBRAL DISC due to aging or structural damage, especially to the vertebral end-plates. Degenerative Disc Disease,Degenerative Intervertebral Discs,Degenerative Intervertebral Disks,Intervertebral Disk Degeneration,Disc Degeneration,Disc Degradation,Disk Degeneration,Disk Degradation,Degeneration, Disc,Degeneration, Disk,Degeneration, Intervertebral Disc,Degeneration, Intervertebral Disk,Degenerative Disc Diseases,Degenerative Intervertebral Disc,Degenerative Intervertebral Disk,Degradation, Disc,Degradation, Disk,Disc Degeneration, Intervertebral,Disc Degenerations,Disc Degradations,Disc Disease, Degenerative,Disc, Degenerative Intervertebral,Disk Degeneration, Intervertebral,Disk Degenerations,Disk Degradations,Disk, Degenerative Intervertebral,Intervertebral Disc Degenerations,Intervertebral Disc, Degenerative,Intervertebral Disk Degenerations,Intervertebral Disk, Degenerative

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