GLUCOSAMINE PREVENTS ABERRANT GENE EXPRESSION OF IL-1BETA IN HUMAN ARTICULAR CHONDROCYTES

Abstract

Osteoarthritis (OA) is a common degenerative disease associated with aging thatas yet has no cure. Glucosamine (Gln) is a naturally produced amino sugar that forms part of the cartilage matrix and is taken by millions of OA sufferers in the hope of alleviating their symptoms. Apart from alleviating pain, there is evidence in the literature that Gln may also be a chondroprotective drug in OA and some clinical trials have shown reduced joint space narrowing in patients taking 1mg Gln per day. However, the mechanisms by which Gln might have its beneficial effects are still uncertain.

We wanted to determine whether Gln has any influence on the aberrant gene expression that takes place in OA chondrocytes. To this end, we cultured healthy articular chondrocytes and induced aberrant gene expression with TNF-α /OSM. Healthy human chondrocytes were isolated from the cartilage of the femoral head obtained after hemiarthroplasty from four patients who had fractured the neck of their femur. Each sample was divided in to 4 groups prior the monolayer culture:

1. Control culture,

2. Gln only,

3. treated with TNF-α/OSM,

4. treated with TNF-α /OSM and Gln.

At confluency (~ 2 weeks) RNA was extracted for analysis of mRNA expression by RT-PCR. The impact of Gln on the expression if the inflammatory cytokine IL-1b and the protease MMP-13 was determined by conventional RT-PCR.

No expression of IL-1b was found in control cultures and Gln on its own did not induce expression. As expected, TNF-a/OSM induced the expression of IL-1b in all four patients. When Gln was present together with TNF-a/OSM, IL-1b expression was prevented in two patients and considerably reduced in the other two patients. With respect to MMP-13, expression was present in 3/4 cultured controls and Gln did not influence this expression. TNF-α /OSM increased expression of IL-1b, and the cytokine-induced expression was slightly reduced by Gln in 2/4 patients.

These results suggest that Gln prevents the TNF-α /OSM-induced expression of IL-1b, but has limited direct influence on MMP-13 expression, at least in vitro. If the data are applicable to the in vivo situations, the results support the proposed chondroprotective effect of glucosamine at the cellular level.