Bone Abstracts

Pioglitazone is a drug of the thiazolidinedione (TZD) class used to treat type 2 diabetes mellitus. TZD is an agonist of peroxisome proliferator-activated receptor γ (PPAR-γ) that improves insulin sensitivity, glucose and lipid metabolism and inflammation. However, TZD induces bone marrow adiposity with suppression of osteogenesis, that could contribute to bone loss and osteoporotic fractures. β-Cryptoxanthin is a carotenoid with antioxidant properties abundant in fruits and vegetables, with stimulatory effects on osteoblastogenesis and inhibitory effects on adipogenesis. In this study it was investigated whether the β-cryptoxanthin may reduce the effect of pioglitazone on bone marrow stromal cell (BMSC) differentiation into osteoblasts. BMSC were induced to differentiate into osteoblasts with dexamethasone, ascorbic acid and glycerol phosphate, in presence or absence of 10⁻⁵ and 10⁻⁴ M pioglitazone or 10⁻⁷ and 10⁻⁶ M cryptoxanthin, or combinations of both. The cultures were maintained until 18 days and samples were taken at different times to study markers gene expression of osteoblastogenesis and adipogenesis, besides of the mineralization of the extracellular matrix. Results show that mainly 10⁻⁴ M pioglitazone blunted mineralization and repressed the expression of osteogenic genes, as runx2, osterix, col1a1 and bsp, after 18 days of treatment, inducing the expression of adipogenic genes, as the ppary and lipoprotein lipase, all the time. This surprisingly favors the presence of cells with adipocyte phenotype in BMSC induced to differentiate into osteoblasts. When the cells were treated with pioglitazone in presence of β-cryptoxanthin, the osteoblastogensis was not decreased. However, the β-cryptoxanthin had no a significant effect on the expression of the adipogenic genes. As a conclusion, the β-cryptoxanthin has a partial positive effect on the differentiation of BMSC into osteoblasts treated with pioglitazone. Therefore, the β-cryptoxanthin could be used to minimize the antiosteoblastic effects of the pioglitazone in type 2 diabetes mellitus patients treated with pioglitazone.