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Natural chondroitin sulphates increase aggregation of proteoglycan complexes and decrease ADAMTS-5 expression in

K Tahiri¹, C Korwin-Zmijowska, P Richette

¹INSERM, UMR-747, Université Paris Descartes, Paris, F-75006, France.

Annals of the Rheumatic Diseases

|September 29, 2007

Summary

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Glycosaminoglycans

Glycosaminoglycans

Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are long and linear polymers comprising of specific repeating disaccharides - the amino sugar that can be N-acetylglucosamine or N-acetylgalactosamine, and a uronic acid that is usually glucuronic acid or iduronic acid.
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...

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Natural chondroitin sulphate (CS) enhances sulphated proteoglycan (PG) production in chondrocytes. CS also partially prevents PG disaggregation caused by interleukin-1 beta (IL1β), linked to reduced ADAMTS-5 expression.

Area of Science:

Biochemistry
Cell Biology
Biomaterials Science

Background:

Interleukin-1 beta (IL1β) is implicated in cartilage degradation by promoting the breakdown of proteoglycans (PGs).
Chondroitin sulphate (CS) is a key component of cartilage extracellular matrix, essential for PG structure and function.
Understanding how exogenous CS affects PG synthesis and stability in chondrocytes under inflammatory conditions is crucial for cartilage health research.

Purpose of the Study:

To investigate the impact of natural chondroitin sulphate (CS) on the aggregation of newly synthesized sulphated proteoglycans (PGs).
To assess CS's effect in cultured chondrocytes stimulated with interleukin-1 beta (IL1β), a pro-inflammatory cytokine.
To elucidate the molecular mechanisms underlying CS's influence on PG metabolism and cartilage matrix integrity.

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Main Methods:

Primary rabbit articular chondrocytes were cultured and treated with IL1β, CS, or both.
Newly synthesized PGs were labeled with [35SO4]-sulphate and analyzed using Sepharose 2B chromatography.
Gene and protein expression of matrix metalloproteinases (MMPs), ADAMTS-4, and ADAMTS-5 were quantified via real-time PCR and Western blotting.

Main Results:

CS significantly increased the production of sulphated PGs within the cellular pool.
CS partially inhibited the IL1β-induced disaggregation of sulphated PGs.
This protective effect correlated with a significant reduction in ADAMTS-5 expression at both mRNA and protein levels.

Conclusions:

In vitro, chondroitin sulphate (CS) promotes the synthesis of functional sulphated proteoglycans (PGs) in chondrocytes.
CS demonstrates a beneficial role in mitigating IL1β-induced PG disaggregation.
The observed benefits of CS are associated with the downregulation of ADAMTS-5, a key enzyme in cartilage matrix degradation.