Articular chondrocytes exist in an environment lacking in
oxygen and nutrients due to the avascular nature of cartilage. The main source of metabolic energy is
glucose, which is taken up by
glucose transporters (GLUTs). In diseased joints,
oxygen tensions and
glucose availability alter as a result of
inflammation and changes in vascularisation. Accordingly, in this study we examined the effects of
hypoxia and the
hypoxia mimetic
cobalt chloride (
CoCl(2)) on
glucose transport in equine chondrocytes and compared expression of the
hypoxia responsive GLUT1 gene in normal and diseased cartilage. Monolayers of equine chondrocytes were exposed to 20% O(2), 1% O(2),
CoCl(2) (75 microM), or a combination of 1% O(2) and
CoCl(2).
Glucose uptake was measured using 2-deoxy-D-[2,6-(3)H]
glucose.
GLUT1 protein and
mRNA expression were determined by FACS analysis and qPCR, respectively. GLUT1
mRNA expression in normal and diseased cartilage was analyzed using explants derived from normal, OA, and OCD cartilage. Chondrocytes under hypoxic conditions exhibited a significantly increased
glucose uptake as well as upregulated
GLUT1 protein expression. GLUT1
mRNA expression significantly increased in combined hypoxia-CoCl(2) treatment. Analysis of clinical samples indicated a significant reduction in GLUT1
mRNA in OA samples. In OCD samples GLUT1 expression also decreased but did not reach statistical significance. The increase in
glucose uptake and GLUT1 expression under hypoxic conditions confirms that
hypoxia alters the metabolic requirements of chondrocytes. The altered GLUT1
mRNA expression in diseased cartilage with significance in OA suggests that reduced GLUT1 may contribute to the failure of OA cartilage repair.