Alterations of Extracellular Matrix Components in the Course of Juvenile Idiopathic Arthritis.

Magdalena Wojdas,Katarzyna Winsz-Szczotka,Klaudia Dąbkowska

doi:10.3390/metabo11030132

Magdalena Wojdas, Katarzyna Winsz-Szczotka + Show 1 more

Open Access

https://doi.org/10.3390/metabo11030132

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Journal: Metabolites	Publication Date: Feb 25, 2021
Citations: 13	License type: CC BY 4.0

Affiliation: Medical University of Silesia

Abstract

Juvenile idiopathic arthritis (JIA) is the most common group of chronic connective tissue diseases in children that is accompanied by joint structure and function disorders. Inflammation underlying the pathogenic changes in JIA, caused by hypersecretion of proinflammatory cytokines, leads to the destruction of articular cartilage. The degradation which progresses with the duration of JIA is not compensated by the extent of repair processes. These disorders are attributed in particular to changes in homeostasis of extracellular matrix (ECM) components, including proteoglycans, that forms articular cartilage. Changes in metabolism of matrix components, associated with the disturbance of their degradation and biosynthesis processes, are the basis of the progressive wear of joint structures observed in the course of JIA. Clinical evaluation and radiographic imaging are current methods to identify the destruction. The aim of this paper is to review enzymatic and non-enzymatic factors involved in catabolism of matrix components and molecules stimulating their biosynthesis. Therefore, we discuss the changes in these factors in body fluids of children with JIA and their potential diagnostic use in the assessment of disease activity. Understanding the changes in ECM components in the course of the child-hood arthritis may provide the introduction of both new diagnostic tools and new therapeutic strategies in children with JIA.

Highlights

Juvenile idiopathic arthritis (JIA) is the most common group of chronic connective tissue diseases in children that is accompanied by joint structure and function disorders
The results indicate that a high level of insulin-like growth factor 1 (IGF-1) in synovial fluid (SF) may be caused by injuries and tissue damage, which results in a local increase in IGF-1 production
In the course of JIA, there occurred a dysregulation of cartilaginous Extracellular matrix (ECM) remodeling, especially aggrecan, manifested by significant changes of the circulating markers of cartilage turnover, including total glycosaminoglycans and their particular types such as keratan sulphate, chondroitin sulphate, hyaluronic acid as well as chondroitin sulphate 846 epitope [54,73,81]

Summary

Introduction

Juvenile idiopathic arthritis (JIA) is the most common group of chronic connective tissue diseases in children that is accompanied by joint structure and function disorders. Pro-inflammatory cytokines lead to the destruction of articular cartilage, which progresses with the duration of JIA, not compensated by the extent of repair processes [15,16,17]. These disorders are attributed in particular to changes in homeostasis of extracellular matrix components of the connective tissue that forms articular cartilage. The changes in metabolism of matrix components, associated with the disturbance of their degradation and biosynthesis processes, are the basis of the progressive wear of joint structures observed in the course of JIA. The main enzymes involved in the process of PGs protein core digestion are matrix metalloproteinases (MMPs) and ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) proteins [30,31,32,33]

Matrix Metalloproteinases

ADAM and ADAMTS

Reactive Oxygen and Nitrogen Species

Anabolic Changes in ECM

Findings

Conclusions