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Vet Comp Orthop Traumatol 2003; 16(02): 93-98
DOI: 10.1055/s-0038-1632759
Original Research
Schattauer GmbH

Polysulphated glycosaminoglycans modulate transcription of interleukin-1β treated chondrocytes in monolayer culture

W. D. Mertens   *
1   College of Veterinary Medicine and the James A. Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853
,
J. N. MacLeod
1   College of Veterinary Medicine and the James A. Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853
,
S. L. Fubini
1   College of Veterinary Medicine and the James A. Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853
,
M. Vernier-Singer
1   College of Veterinary Medicine and the James A. Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853
,
A. J. Nixon
1   College of Veterinary Medicine and the James A. Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853
,
R. J. Todhunter
1   College of Veterinary Medicine and the James A. Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853
› Author AffiliationsThe authors thank Lisa Fortier, DVM, PhD, DACVS for critical technical assistance.
Further Information

Publication History

Received 10 May 2002

Accepted 01 September 2002

Publication Date:
22 February 2018 (online)

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Summary

The ability of polysulphated glycosaminoglycans (PSGAGs, Adequan®) to modulate the transcription of major articular cartilage matrix proteins and enzymes was examined. Northern blot analyses were used to compare steady-state mRNA levels of type-II procollagen, aggrecan core protein, matrix metalloproteinase (MMP)-1, MMP-3, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-3 in equine chondrocytes grown in monolayer culture. The groups included: control, low-dose (0.1mg/ml) Adequan®, high-dose (1.0mg/ml) Adequan®, IL-1 β (10ng/ml), IL-1 β with low-dose Adequan®, and IL-1 β with high-dose Adequan®. The responses (p<0.05) to treatment were compared with one-way analysis of variance and post hoc least significant difference test. Interleukin-1 β significantly decreased steady-state levels of type-II procollagen (0.5x) and aggrecan core protein (to undetectable levels) and significantly increased MMP-1 (11.7x), MMP-3 (1.8x), TIMP-1 (1.9x), and TIMP-3 (5.1 x). Adequan® alone significantly increased steady-state mRNA levels of type-II procollagen (1.6x) and decreased MMP-1 (0.3x at high-dose only), MMP-3 (0.5x), and TIMP-1 (0.3x at high-dose only). In IL-1 β-treated chondrocytes, Adequan® significantly increased steady-state mRNA levels of type-II procollagen (1.4x of IL-1 β-treated levels), aggrecan core protein (IL-1 β -treated had no detectable expression), and MMP-3 (3.6 x at high dose) and significantly decreased steady-state mRNA levels of MMP-1 (0.3 x), and TIMP-1 (0.2x). This study is the first to demonstrate that Adequan® alters steady-state mRNA levels of key matrix proteins and enzymes; that it counteracts some of the deleterious effects of IL-1 β; and that these effects are in part dose-dependent.

Keywords

Chondrocyte - mRNA - polysulphated glycosaminoglycan - interleukin-1 - equine

* Current Address: MS 4474, Texas A&M University, College Station, TX 77843 USA


 

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