Osteogenic differentiation of bone marrow mesenchymal stem cells of ovariectomized and non-ovariectomized female rats with thyroid dysfunction

The objective of this study was to verify the osteogenic potential of the bone marrow mesenchymal stem cells (MSCs) of ovariectomized and non-ovariectomized female rats with hypo- and hyperthyroidism. Sixty two-month-old female rats were assigned to the following groups: (1) control (sham-operated), (2) ovariectomized (OVX’d), (3) hypothyroid sham-operated (Hypo-), (4) hypothyroid OVX’d, (5) hyperthyroid sham-operated (Hyper-) and (6) hyperthyroid OVX’d. After 135 days of treatment, the female rats were euthanized. We collected plasma to measure the levels of free T4, and the femur for extraction of MSCs. At 7 and 21 days of osteogenic differentiation of MSCs, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) conversion, alkaline phosphatase activity, mineralized nodule number and gene expression for collagen I, osteocalcin, bone sialoprotein and osteopontin were analyzed. The hypothyroid group presented a significant reduction in the osteogenic differentiation of MSCs. The hyperthyroid group did not present changes in the synthesis of mineralized nodules for MSCs at day 21 of differentiation. However, in ovariectomized rats, hyperthyroidism increased the osteogenic differentiation of MSCs characterized by the increase of the alkaline phosphatase activity, the number of mineralized nodules and the expression of osteocalcin, sialoprotein and osteopontin. Our results demonstrated that the hypothyroidism reduces the osteogenic differentiation of MSCs only in non-ovariectomized rats and that the hyperthyroidism increases the osteogenic differentiation of MSCs only in ovariectomized rats.