Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes.
Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes.
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DOI：
10.1210/endo.140.4.6637
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发表时间：
1999-04
期刊：
影响因子：
4.8
通讯作者：
T. Thomas;F. Gori;S. Khosla;M. Jensen;B. Burguera;B. Riggs
中科院分区：
文献类型：
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作者：
T. Thomas;F. Gori;S. Khosla;M. Jensen;B. Burguera;B. Riggs
肥胖者的骨量和血清瘦素水平均升高。由于成骨细胞和脂肪细胞来自骨髓中的共同前体，我们评估了人重组瘦素对条件永生化人骨髓基质细胞系hMS 2 -12的影响，该细胞系具有分化为成骨细胞或脂肪细胞表型的潜力。通过RT-PCR和Western免疫印迹分析，hMS 2 -12细胞表达瘦素受体的信使RNA（mRNA）和蛋白。瘦素不影响hMS 2 -12细胞增殖，但导致碱性磷酸酶，I型胶原和骨钙素的mRNA和蛋白水平的剂量和时间依赖性增加，并在矿化基质增加59%。瘦素在第3天增加脂蛋白脂肪酶的mRNA水平，但在第9天降低脂蛋白酶和瘦素的mRNA水平，并减少50%的脂滴形成。瘦素不影响Cbfa 1或过氧化物酶体增殖物激活受体-γ 2的表达，转录因子参与承诺成骨细胞和脂肪细胞途径，分别。因此，瘦素作用于人骨髓基质细胞，增强成骨细胞分化并抑制脂肪细胞分化。我们的数据支持这一假设，瘦素是一个以前未被认识到的，这两个分化途径的生理调节，主要作用于成熟的基质细胞成两个谱系。
Both bone mass and serum leptin levels are increased in obesity. Because osteoblasts and adipocytes arise from a common precursor in bone marrow, we assessed the effects of human recombinant leptin on a conditionally immortalized human marrow stromal cell line, hMS2-12, with the potential to differentiate to either the osteoblast or adipocyte phenotypes. By RT-PCR and Western immunoblot analysis, the hMS2-12 cells expressed messenger RNA (mRNA) and protein for the leptin receptor. Leptin did not affect hMS2-12 cell proliferation, but resulted in dose- and time-dependent increases in mRNA and protein levels of alkaline phosphatase, type I collagen, and osteocalcin, and in a 59% increase in mineralized matrix. Leptin increased mRNA levels of lipoprotein lipase at 3 days, but decreased mRNA levels of adipsin and leptin at 9 days and decreased lipid droplet formation by 50%. Leptin did not affect the expression of Cbfa1 or peroxisome proliferator-activated receptor-gamma2, transcription factors involved in commitment to the osteoblast and adipocyte pathways, respectively. Thus, leptin acts on human marrow stromal cells to enhance osteoblast differentiation and to inhibit adipocyte differentiation. Our data support the hypothesis that leptin is a previously unrecognized, physiological regulator of these two differentiation pathways, acting primarily on maturation of stromal cells into both lineages.