Rodríguez J Pablo, Astudillo Pablo, Ríos Susana, Pino Ana María
Laboratorio de Biología Celular, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Macul 5540, Macul. Casilla 138-11, Santiago, Chile.
Curr Stem Cell Res Ther. 2008 Sep;3(3):208-18. doi: 10.2174/157488808785740325.
Mesenchymal Stem Cells (MSCs) from bone marrow stroma are capable of differentiating into osteoblasts and adipocytes, among other cell phenotypes. In normal bone marrow osteoblastic and adipocytic cell differentiation occur in favor of bone formation, but this relationship appears disrupted in several bone diseases. In osteoporosis increased bone marrow adipocyte production is counterbalanced by diminished production of osteogenic cells. Since osteoblasts and adipocytes originate from a common MSC precursor cell, quantitative and qualitative stem cell defects may underlie the modified number and function of differentiated cells. This review analyzes experimental evidence which describes differences in the osteogenic/adipogenic potentials of human bone marrow MSCs obtained from control and osteoporotic postmenopausal women. The protective effect exerted by locally generated factors, such as estradiol and leptin, on MSCs differentiation was analyzed, because altered bioavailability of these factors may play a part in osteoporosis triggering. Several properties differ among differentiating MSCs from control and osteoporotic donors. Some of these functional differences may be considered to mirror, at the cell level, the detrimental changes displayed in osteoporosis. Osteoporotic MSCs are characterized by increased adipogenic potential, as shown by increased PPARgamma protein content and diminished inactivation of the transcription factor, as compared to control cells. Leptin exerts a direct protective activity against adipogenesis only in control cells. In contrast, leptin activity in MSCs from osteoporotic women appears hampered, suggesting that inadequate leptin activity contributes to excessive lipid accumulation in bone marrow.
来自骨髓基质的间充质干细胞（MSC）能够分化为成骨细胞和脂肪细胞等多种细胞表型。在正常骨髓中，成骨细胞和脂肪细胞的分化有利于骨形成，但这种关系在几种骨疾病中似乎被破坏。在骨质疏松症中，骨髓脂肪细胞生成增加，而成骨细胞生成减少，两者相互抵消。由于成骨细胞和脂肪细胞起源于共同的MSC前体细胞，干细胞的数量和质量缺陷可能是分化细胞数量和功能改变的基础。本综述分析了实验证据，这些证据描述了从对照和绝经后骨质疏松症女性获得的人骨髓MSC在成骨/成脂潜能方面的差异。分析了局部产生的因子，如雌二醇和瘦素，对MSC分化的保护作用，因为这些因子生物利用度的改变可能在骨质疏松症的引发中起作用。对照和骨质疏松症供体的分化MSC之间存在一些差异。其中一些功能差异可能被认为在细胞水平上反映了骨质疏松症中出现的有害变化。与对照细胞相比，骨质疏松症MSC的特征是成脂潜能增加，表现为PPARγ蛋白含量增加和转录因子失活减少。瘦素仅在对照细胞中对脂肪生成具有直接保护活性。相比之下，骨质疏松症女性的MSC中的瘦素活性似乎受到阻碍，这表明瘦素活性不足导致骨髓中脂质过度积累。
