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

Abstract

SummaryThe 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.

Effects of treatment with polysulfated glycosaminoglycan on serum cartilage oligomeric matrix protein and C-reactive protein concentrations, serum matrix metalloproteinase-2 and -9 activities, and lameness in dogs with osteoarthritis

“…3,26,27 The mechanism of action of PSGAG is considered to be an acceleration of extracellular matrix production by stimulation of chondrocytes and synoviocytes, inhibition of proteolytic enzymes, and the production of inflammatory mediators. 3,35,36 Polysulfated glycosaminoglycan has potential use for pain modification in arthropathy and for inhibition of cartilage matrix degradation. The pharmacologic action of PSGAG appears to involve the repair of damaged joint cartilage, inhibition of proteoglycan degradation, and an anti-inflammatory effect when distributed to damaged articular cartilage, protecting against loss of proteoglycan from the articular cartilage.…”

“…The pharmacologic action of PSGAG appears to involve the repair of damaged joint cartilage, inhibition of proteoglycan degradation, and an anti-inflammatory effect when distributed to damaged articular cartilage, protecting against loss of proteoglycan from the articular cartilage. 3,5,27,35,36 Also, PSGAG inhibits the degradation of articular cartilage and inflammation of periarticular tissue through inhibition of MMP activity, collagenolytic enzyme activity, or both as well as inhibition of nitric oxide production from inflammatory cells. 37 Administration of PSGAG is a useful adjunctive treatment for osteoarthritis in dogs and horses but is not a panacea.…”