FK506 Induces the TGF-β1/Smad 3 Pathway Independently of Calcineurin Inhibition to Prevent Intervertebral Disk Degeneration

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2020 Dec 28

PMID 33363168

Citations 3

Authors

Jun Ge

Yingjie Wang

Qi Yan

Cenhao Wu

Hao Yu

Huilin Yang

Jun Zou

Affiliations

Soon will be listed here.

Abstract

Background: Intervertebral disk (IVD) degeneration is the most common cause of lower back pain. Inhibiting inflammation is a key strategy for delaying IVD degeneration. Tacrolimus (FK506) is a potent immunosuppressive agent that is also beneficial to chondrocytes via alleviating inflammation. However, the potential function of FK506 in IVD and the underlying mechanisms remain unknown. The current study is aim at exploring the underlying mechanism of FK506 in preventing IVD degeneration.

Methods: Cell morphology was imaged using an optical microscope. mRNA levels of nucleus pulposus (NP) matrix components were determined by qRT-PCR, and protein expression NP matrix components was assessed by western blotting. A rat caudal IVD degeneration model was established to test for FK506 .

Results: FK506 improved the morphology of NP cells and the cell function at both the mRNA and protein level. FK506 could attenuate NP degeneration induced by IL-1β. Furthermore, FK506 exerted its function via TGFβ/Smad3 activation instead of through calcineurin inhibition. Inhibition of the TGF-β pathway prevented the protective effect of FK506 on IVD degeneration. In an study, FK506 injection reversed the development of rat caudal IVD degeneration influenced by Smad3.

Conclusion: Our current study demonstrates the positive effect of FK506 on delaying the degeneration of IVD via the TGFβ/Smad3 pathway.

Citing Articles

Development and Validation of a Novel Nomogram to Predict the Risk of Intervertebral Disc Degeneration.

Li F, Sun X, Wang Y, Gao L, Shi J, Sun K Mediators Inflamm. 2022; 2022:3665934.

PMID: 36123994 PMC: 9482533. DOI: 10.1155/2022/3665934.

Physosmotic Induction of Chondrogenic Maturation Is TGF-β Dependent and Enhanced by Calcineurin Inhibitor FK506.

Jahr H, Windt A, Timur U, Baart E, Lian W, Rolauffs B Int J Mol Sci. 2022; 23(9).

PMID: 35563498 PMC: 9100228. DOI: 10.3390/ijms23095110.

Hydroxysafflor yellow A attenuates oxidative stress injury-induced apoptosis in the nucleus pulposus cell line and regulates extracellular matrix balance via CA XII.

Yang S, Liao W Exp Ther Med. 2022; 23(2):182.

PMID: 35069863 PMC: 8764902. DOI: 10.3892/etm.2021.11105.

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