Abstract
The increased incidence of type 2 Diabetes Mellitus is associated with an impaired skeletal structure and a higher prevalence of bone fractures. Sclerostin is a negative regulator of bone formation produced by osteocytes and there is recent evidence that its expression in serum is elevated in diabetic patients compared to control subjects. In this study, we test whether hyperglycemia affects serum and bone sclerostin levels in a rat model of type 2 Diabetes as well as sclerostin production by osteoblasts in culture.
We used Zucker diabetic fatty (ZDF) male rats (n=6) that spontaneously develop obesity and frank diabetes around 8–9 weeks of age and Zucker lean rats as controls (n=6) to examine sclerostin expression in serum at 9, 11 and 13 weeks using a specific ELISA. Sclerostin expression in bone tibiae was examined at 12 weeks using immunocytochemistry. Rat osteoblast-like cells UMR-106 were cultured in the presence of increasing concentrations of glucose (5, 11, 22 and 44 mM) during 48 hours and sclerostin mRNA expression and release in the supernatant determined by quantitative PCR and ELISA, respectively.
Our results show that serum sclerostin levels are higher in the diabetic rats compared to lean rats at 9 weeks (+ 140%, p<0.01). Our preliminary results using immunocytochemistry for sclerostin did not show any major difference in sclerostin expression in tibiae of diabetic rats compared to lean ones, although we observed many osteocytic empty lacunae in cortical bone from diabetic rats. Glucose dose-dependent stimulated sclerostin mRNA and protein production in mature UMR106 cells while it had no effect on osteocalcin expression.
Altogether, our data suggest that sclerostin production by mature osteoblasts is increased by hyperglycemia in vitro and enhanced in serum of diabetic rats. Furthers studies are required to determine whether sclerostin could contribute to the deleterious effect of Diabetes on bone.
