Antiaging Factor Klotho Retards the Progress of Intervertebral Disc Degeneration Through the Toll-Like Receptor 4-NF-B Pathway

Overview

Journal Int J Cell Biol

Publisher Wiley

Specialty Cell Biology

Date 2020 Apr 8

PMID 32256598

Citations 13

Authors

Fangfang Bi

Wenbo Liu

Zongtao Wu

Chen Ji

Cuicui Chang

Affiliations

Soon will be listed here.

Abstract

Antiaging protein Klotho exhibits impressive properties of anti-inflammation, however is declined early after intervertebral disc injury, making Klotho restoration an attractive strategy of treating intervertebral disc inflammatory disorders. Here, we have found that Klotho is enriched in nucleus pulposus (NP) cells and Klotho overexpression attenuates HO-induced acute inflammation essentially via suppressing Toll-like receptor 4 (TLR4). The proinflammatory NF-B signaling and cytokine expressions paralleled with Klotho repression and TLR4 elevation in both NP cells (HO treatment) and rat intervertebral disc (needle puncture treatment). Overexpression of TLR4 downregulated expression of Klotho, whereas interfering TLR4 expression diminished the inhibitory effects of HO on Klotho in NP cells. Consistently, Klotho knockdown by RNA interferences largely diminished the anti-inflammatory and intervertebral disc protective effects in an Intervertebral Disc Degeneration (IDD) model. Thus, our study indicates that TLR4-NF-B signaling and Klotho form a negative-feedback loop in NP cells. Also, we demonstrate that the expression of Klotho is regulated by the balance between upregulation and downregulation of TLR4-NF-B signaling.

Citing Articles

Targeting skeletal interoception: a novel mechanistic insight into intervertebral disc degeneration and pain management.

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Klotho mutation does not accelerate intervertebral disc aging in mice.

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New insights into the role of Klotho in inflammation and fibrosis: molecular and cellular mechanisms.

Zhao X, Han D, Zhao C, Yang F, Wang Z, Gao Y Front Immunol. 2024; 15:1454142.

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Anti-Inflammatory Role of the Klotho Protein and Relevance to Aging.

Prudhomme G, Wang Q Cells. 2024; 13(17.

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