Lysyl oxidase suppresses the inflammatory response in anterior cruciate ligament fibroblasts and promotes tissue regeneration by targeting myotrophin via the nuclear factor-kappa B pathway.
Anterior Cruciate Ligament
/ physiology
Anterior Cruciate Ligament Injuries
/ metabolism
Fibroblasts
/ metabolism
Humans
Inflammation
/ metabolism
Intercellular Signaling Peptides and Proteins
/ metabolism
NF-kappa B
/ metabolism
Protein-Lysine 6-Oxidase
/ metabolism
Regeneration
Signal Transduction
ACL regeneration
RNA sequencing
anti-inflammation
molecular target
new function
Journal
Journal of tissue engineering and regenerative medicine
ISSN: 1932-7005
Titre abrégé: J Tissue Eng Regen Med
Pays: England
ID NLM: 101308490
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
03
12
2019
revised:
04
05
2020
accepted:
11
05
2020
pubmed:
3
6
2020
medline:
12
8
2021
entrez:
3
6
2020
Statut:
ppublish
Résumé
Anterior cruciate ligament (ACL) regeneration is severely affected by the injury-induced overexpression of matrix metalloproteinases (MMPs) and downregulation of lysyl oxidase (LOX). Previous studies have focused on how the expression of MMPs and downregulation of LOX are physiologically balanced at injured sites for regenerating the ACL tissue, but the role of LOX in regulating cellular functions has not been investigated yet. Herein, we conducted an in vitro cellular experiment and unexpectedly found that exogenous LOX inhibited the expression of MMPs and inflammatory factors and recovered the cell growth; thus, LOX strongly inhibited the tumor necrosis factor-alpha (TNF-α)-induced inflammatory responses. In an in vivo animal model, LOX supplementation suppressed the expression of TNF-α in injured ACLs and promoted the recovery of the damaged tissues. RNA-sequencing-identified differentially expressed genes (DEGs) were highly enriched in the nuclear factor-kappa B (NF-κB), chemokine, cytokine-cytokine receptor interaction, Toll-like receptor, and TNF signaling pathways. Immunofluorescence tracing was employed to localise the exogenous LOX in the cell nucleus; the exogenous LOX indirectly suggests that it has other biological roles apart from the cross-linking of the extracellular matrix. Protein-protein interaction network analysis revealed the anti-inflammatory effect of LOX was alleviated by silencing the myotrophin (MTPN) expression, suggesting that LOX might interact with MTPN and regulate inflammation. Finally, this study suggests that LOX can inhibit the inflammatory response of ACL fibroblasts (ACLfs) and promote the recovery of the damaged ACL tissue through the MTPN-mediated NF-κB signaling pathway.
Substances chimiques
Intercellular Signaling Peptides and Proteins
0
NF-kappa B
0
myotrophin
0
LOX protein, human
EC 1.4.3.13
Protein-Lysine 6-Oxidase
EC 1.4.3.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1063-1076Informations de copyright
© 2020 John Wiley & Sons, Ltd.
Références
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