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Thrombospondin-1 promotes mechanical stress-mediated ligamentum flavum hypertrophy through the TGFβ1/Smad3 signaling pathway.

Authors :
Zhao R
Dong J
Liu C
Li M
Tan R
Fei C
Chen Y
Yang X
Shi J
Xu J
Wang L
Li P
Zhang Z
Source :
Matrix biology : journal of the International Society for Matrix Biology [Matrix Biol] 2024 Mar; Vol. 127, pp. 8-22. Date of Electronic Publication: 2024 Jan 26.
Publication Year :
2024

Abstract

Lumbar spinal canal stenosis is primarily caused by ligamentum flavum hypertrophy (LFH), which is a significant pathological factor. Nevertheless, the precise molecular basis for the development of LFH remains uncertain. The current investigation observed a notable increase in thrombospondin-1 (THBS1) expression in LFH through proteomics analysis and single-cell RNA-sequencing analysis of clinical ligamentum flavum specimens. In laboratory experiments, it was demonstrated that THBS1 triggered the activation of Smad3 signaling induced by transforming growth factor β1 (TGFβ1), leading to the subsequent enhancement of COL1A2 and α-SMA, which are fibrosis markers. Furthermore, experiments conducted on a bipedal standing mouse model revealed that THBS1 played a crucial role in the development of LFH. Sestrin2 (SESN2) acted as a stress-responsive protein that suppressed the expression of THBS1, thus averting the progression of fibrosis in ligamentum flavum (LF) cells. To summarize, these results indicate that mechanical overloading causes an increase in THBS1 production, which triggers the TGFβ1/Smad3 signaling pathway and ultimately results in the development of LFH. Targeting the suppression of THBS1 expression may present a novel approach for the treatment of LFH.<br />Competing Interests: Declaration of competing interest All authors have approved the manuscript and agree with its submission. The authors have no conflicts of interests to declare.<br /> (Copyright © 2024. Published by Elsevier B.V.)

Details

Language :
English
ISSN :
1569-1802
Volume :
127
Database :
MEDLINE
Journal :
Matrix biology : journal of the International Society for Matrix Biology
Publication Type :
Academic Journal
Accession number :
38281553
Full Text :
https://doi.org/10.1016/j.matbio.2024.01.005