Dual Effects of 17ß-oestradiol on Interleukin 1ß-induced Proteoglycan Degradation in Chondrocytes

Richette, P., Dumontier, M. F., Francois, M., Tsagris, L ., Korwin-Zmijowska, C., Rannou, F and Corvol, M. T. (2004) Dual Effects of 17ß-oestradiol on Interleukin 1ß-induced Proteoglycan Degradation in Chondrocytes. Annals of the Rheumatic Diseases, 63 2: 191-199. doi:10.1136/ard.2003.006510

Author Richette, P.
Dumontier, M. F.
Francois, M.
Tsagris, L .
Korwin-Zmijowska, C.
Rannou, F
Corvol, M. T.
Title Dual Effects of 17ß-oestradiol on Interleukin 1ß-induced Proteoglycan Degradation in Chondrocytes
Journal name Annals of the Rheumatic Diseases   Check publisher's open access policy
ISSN 0003-4967
Publication date 2004-02
Sub-type Article (original research)
DOI 10.1136/ard.2003.006510
Volume 63
Issue 2
Start page 191
End page 199
Total pages 9
Place of publication London
Publisher BMJ
Language eng
Subject 060405 Gene Expression (incl. Microarray and other genome-wide approaches)
Abstract Objective: To determine whether 17ß-oestradiol (E2) modulates interleukin (IL) 1ß-induced proteoglycan degradation in chondrocytes, and to analyse the part played by metalloproteinases (MMPs) in this process. Methods: Primary cultured rabbit articular chondrocytes were prepared and treated with 10 ng/ml IL1ß combined or not with 0.1–10 nM E2. Neosynthesised proteoglycans (PGs) were evaluated after incorporation of [35SO4]sulphate and further analysed after chromatography on a Sepharose 2B column. Chondrocyte mRNA levels of aggrecan, MMP-1, -3, -13, and tissue inhibitor of metalloproteinase-1 (TIMP-1) were studied by northern blot. MMP-1 activity was measured by zymography. MMP-1 gene transcription was studied by transient transfection of chondrocytes with an MMP-1-luciferase construct. Results: E2 modulated the IL1ß-induced total sulphated PGs in rabbit articular chondrocytes, which decreased as the E2 concentration was increased. At a low concentration (0.1 nmol/l) E2 counteracts the IL1ß-induced decrease in sulphated PG, while at high concentration (10 nmol/l) E2 enhances the IL1ß effects. A biphasic E2 effect was also observed on IL1ß-induced disaggregation of PG, 53–58 kDa gelatinolytic activity, and MMP-1, -3, and -13 mRNA levels. In contrast, E2 did not modify the level of aggrecan mRNA and had no effect on TIMP-1 mRNA expression. Finally, simultaneous addition of IL1ß and E2 (0.1–10 nmol/l) did not modify IL1ß-induced MMP-1-luciferase activity, suggesting that E2 effects probably occur at the post-transcriptional level of MMP gene expression. Conclusion: Oestrogen concentration may have an inverse effect on IL1ß stimulated proteoglycan degradation and MMP production by chondrocytes.
Keyword Rheumatism
Joints - Diseases
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
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