Hess Rodrigo, Pino Ana María, Ríos Susana, Fernández Mireya, Rodríguez J Pablo
Laboratorio de Biología Celular, INTA, Universidad de Chile, Casilla 138-11, Santiago, Chile.
J Cell Biochem. 2005 Jan 1;94(1):50-7. doi: 10.1002/jcb.20330.
There are disparate observations on central and peripheral effects of leptin, but several studies consistently support its role as a link between fat and bone. Bone marrow stroma contains mesenchymal stem cells (MSCs), which differentiate into osteoblasts and adipocytes, among others. In this study we assessed the expression of leptin receptors protein in MSCs from control and osteoporotic postmenopausal donors and their change during osteogenic and adipogenic differentiation. Also, we assessed the effects of leptin on osteogenic and adipogenic differentiation of these cells. We demonstrated high affinity leptin binding (KD = 0.36 +/- 0.02 nM) in both types of cells. Binding was very low under basal, but increased significantly (2-3 times) through osteogenic and adipogenic differentiation. Osteoporotic MSCs showed lower leptin binding capacity than control cells at an early osteogenic and adipogenic differentiation time, which could restrict cell sensitivity to the protective action of leptin. In this regard, we observed that leptin significantly inhibited adipocyte differentiation in control but not in osteoporotic MSCs, while it exerted a low stimulatory effect on calcium deposition (10%-20%) in both types of MSCs cells. In summary, we report the presence of high affinity leptin receptors on control and osteoporotic MSCs, which were modified distinctly by osteogenic and adipogenic stimulation and a direct and distinct effect of leptin on both type of cells.
关于瘦素的中枢和外周作用存在不同的观察结果，但多项研究一致支持其作为脂肪与骨骼之间联系的作用。骨髓基质包含间充质干细胞（MSC），这些细胞可分化为成骨细胞和脂肪细胞等。在本研究中，我们评估了来自对照和绝经后骨质疏松症供体的MSC中瘦素受体蛋白的表达及其在成骨和成脂分化过程中的变化。此外，我们评估了瘦素对这些细胞成骨和成脂分化的影响。我们证明了两种类型的细胞中均存在高亲和力的瘦素结合（KD = 0.36 +/- 0.02 nM）。基础状态下结合力很低，但在成骨和成脂分化过程中显著增加（2 - 3倍）。在成骨和成脂分化早期，骨质疏松症的MSC显示出比对照细胞更低的瘦素结合能力，这可能会限制细胞对瘦素保护作用的敏感性。在这方面，我们观察到瘦素显著抑制对照MSC中的脂肪细胞分化，但对骨质疏松症的MSC没有作用，而它对两种类型的MSC细胞中的钙沉积均有低刺激作用（10% - 20%）。总之，我们报告了对照和骨质疏松症的MSC上存在高亲和力的瘦素受体，它们在成骨和成脂刺激下有明显改变，并且瘦素对两种类型的细胞有直接且明显的作用。
