Interleukin-1α induces ADAMTS-mediated aggrecanolysis in the bovine meniscus: evidence for a primary role of ADAMTS-4 in meniscus destruction
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Author(s)
Lemke, Angelika K.
Sandy, John D.
Voigt, Henning
Dreier, Rita
Lee, Jennifer H.
Grodzinsky, Alan J.
Mentlein, Rolf
Fay, Jakob
Schunke, Michael
Kurz, Bodo
Alternative Title
Interleukin-1α treatment of meniscal explants stimulates the production and release of aggrecanase-generated, GAG-substituted aggrecan products and also the release of pre-formed, aggrecanase-generated G1 and m-calpain-generated G1-G2
Date Issued
March 2010
Journal
Cell Tissue Research
Publisher
Springer-Verlag
Citation
Lemke, Angelika K. et al. “Interleukin-1α Treatment of Meniscal Explants Stimulates the Production and Release of Aggrecanase-generated, GAG-substituted Aggrecan Products and Also the Release of Pre-formed, Aggrecanase-generated G1 and M-calpain-generated G1-G2.” Cell and Tissue Research 340.1 (2010): 179–188.
Version
Original manuscript
Abstract
Pro-inflammatory cytokines induce meniscal matrix degradation and inhibition of endogenous repair mechanisms, but the pathogenic mechanisms behind this are mostly unknown. Therefore, we investigated details of interleukin-1 (IL-1α)-induced aggrecan turnover in mature meniscal tissue explants. Fibro-cartilagenous disks (3 mm diameter × 1 mm thickness) were isolated from the central, weight-bearing region of menisci from 2-year-old cattle. After 3 or 6 days of IL-1α-treatment, GAG loss (DMMB assay), biosynthetic activity ([35SO4]-sulfate and [3H]-proline incorporation), gene expression (quantitative RT-PCR) and the abundance (zymography, Western blot) of matrix-degrading enzymes and specific aggrecan products were determined. Meniscal fibrocartilage had a 4-fold lower GAG content (per wet weight) than adjacent articular cartilage, and expressed MMPs-1, -2, -3 and ADAMTS4 constitutively, whereas ADAMTS5 m-RNA was essentially undetectable. Significant IL-1 effects were a decrease in biosynthetic activity, an increase in GAG release and in the expression/abundance of MMP-2, MMP-3 and ADAMTS4. Fresh tissue contained aggrecan core protein products similar to those previously described for bovine articular cartilage of this age. IL-1 induced the release of aggrecanase-generated CS-substituted products including both high (>250 kDa) and low molecular weight (about 75 kDa) species. TIMP-3 (but not TIMP-1 and -2 or a broad spectrum MMP inhibitor) inhibited IL-1-dependent GAG loss. In addition, IL-1 induced the release of preformed pools of three known G1-bearing products. We conclude that aggrecanases are responsible for IL-1-stimulated GAG release from meniscal explants, and that IL-1 also stimulates release of G1-bearing products, by a process possibly involving hyaluronan fragmentation.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1007/s00441-010-0941-4
