Departamento de Clínica e Cirurgia Veterinárias, Escola de Veterinária da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Pathol Res Pract. 2013 Jan 15;209(1):44-51. doi: 10.1016/j.prp.2012.10.004. Epub 2012 Nov 17.
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.
本研究旨在验证去势和非去势伴发甲状腺功能减退和甲状腺功能亢进雌性大鼠骨髓间充质干细胞(MSCs)的成骨潜能。将 62 月龄雌性大鼠分为以下几组:(1)对照组(假手术)、(2)去势组(OVX'd)、(3)甲状腺功能减退假手术组(Hypo-)、(4)甲状腺功能减退去势组、(5)甲状腺功能亢进假手术组(Hyper-)和(6)甲状腺功能亢进去势组。治疗 135 天后,处死雌性大鼠。收集血浆以测量游离 T4 水平,并提取股骨中的 MSCs。在 MSC 成骨分化的第 7 和 21 天,分析 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐(MTT)转化率、碱性磷酸酶活性、矿化结节数量以及 I 型胶原、骨钙素、骨涎蛋白和骨桥蛋白的基因表达。甲状腺功能减退组 MSC 的成骨分化显著减少。甲状腺功能亢进组在分化第 21 天,MSC 矿化结节的合成没有变化。然而,在去势大鼠中,甲状腺功能亢进增加了 MSC 的成骨分化,表现为碱性磷酸酶活性、矿化结节数量和骨钙素、涎蛋白和骨桥蛋白的表达增加。我们的研究结果表明,甲状腺功能减退仅在非去势大鼠中减少 MSC 的成骨分化,而甲状腺功能亢进仅在去势大鼠中增加 MSC 的成骨分化。