Role of Hyaluronan in Inflammatory Effects on Human Articular Chondrocytes

Mary Cowman, Claire Shortt, Shivani Arora, Yuhong Fu, Jemma Villavieja, Jai Rathore, Xiayun Huang, Tatini Rakshit, Gyu Ik Jung, Thorsten Kirsch

Research output: Contribution to journalArticle

Abstract

Hyaluronan (HA) fragments have been proposed to elicit defensive or pro-inflammatory responses in many cell types. For articular chondrocytes in an inflammatory environment, studies have failed to reach consensus on the endogenous production or effects of added HA fragments. The present study was undertaken to resolve this discrepancy. Cultured primary human articular chondrocytes were exposed to the inflammatory cytokine IL-1β, and then tested for changes in HA content/size in conditioned medium, and for the expression of genes important in HA binding/signaling or metabolism, and in other catabolic/anabolic responses. Changes in gene expression caused by enzymatic degradation of endogenous HA, or addition of exogenous HA fragments, were examined. IL-1β increased the mRNA levels for HA synthases HAS2/HAS3 and for the HA-binding proteins CD44 and TSG-6. mRNA levels for TLR4 and RHAMM were very low and were little affected by IL-1β. mRNA levels for catabolic markers were increased, while type II collagen (α1(II)) and aggrecan were decreased. HA concentration in the conditioned medium was increased, but the HA was not degraded. Treatment with recombinant hyaluronidase or addition of low endotoxin HA fragments did not elicit pro-inflammatory responses. Our findings showed that HA fragments were not produced by IL-1β-stimulated human articular chondrocytes in the absence of other sources of reactive oxygen or nitrogen species, and that exogenous HA fragments from oligosaccharides up to about 40 kDa in molecular mass were not pro-inflammatory agents for human articular chondrocytes, probably due to low expression of TLR4 and RHAMM in these cells.

Original languageEnglish (US)
JournalInflammation
DOIs
StatePublished - Jan 1 2019

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Hyaluronic Acid
Chondrocytes
Joints
Interleukin-1
Conditioned Culture Medium
Messenger RNA
CD44 Antigens
Gene Expression
Aggrecans
Reactive Nitrogen Species
Hyaluronoglucosaminidase
Collagen Type I
Oligosaccharides
Endotoxins
Reactive Oxygen Species
Cytokines

Keywords

  • articular cartilage
  • chondrocytes
  • hyaluronan
  • hyaluronidase
  • inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Role of Hyaluronan in Inflammatory Effects on Human Articular Chondrocytes. / Cowman, Mary; Shortt, Claire; Arora, Shivani; Fu, Yuhong; Villavieja, Jemma; Rathore, Jai; Huang, Xiayun; Rakshit, Tatini; Jung, Gyu Ik; Kirsch, Thorsten.

In: Inflammation, 01.01.2019.

Research output: Contribution to journalArticle

Cowman, M, Shortt, C, Arora, S, Fu, Y, Villavieja, J, Rathore, J, Huang, X, Rakshit, T, Jung, GI & Kirsch, T 2019, 'Role of Hyaluronan in Inflammatory Effects on Human Articular Chondrocytes', Inflammation. https://doi.org/10.1007/s10753-019-01043-9
Cowman, Mary ; Shortt, Claire ; Arora, Shivani ; Fu, Yuhong ; Villavieja, Jemma ; Rathore, Jai ; Huang, Xiayun ; Rakshit, Tatini ; Jung, Gyu Ik ; Kirsch, Thorsten. / Role of Hyaluronan in Inflammatory Effects on Human Articular Chondrocytes. In: Inflammation. 2019.
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AU - Rathore, Jai

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AU - Kirsch, Thorsten

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