Exposure of KS483 cells to estrogen enhances osteogenesis and inhibits adipogenesis
Exposure of KS483 cells to estrogen enhances osteogenesis and inhibits adipogenesis
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DOI：
10.1359/jbmr.2002.17.3.394
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发表时间：
2002-03-01
影响因子：
6.2
通讯作者：
Löwik, CWGM
中科院分区：
文献类型：
--
作者：
Dang, ZC;Van Bezooijen, RL;Löwik, CWGM
成骨细胞和脂肪细胞起源于骨髓中的同一祖细胞。雌激素是否直接调节祖细胞向成骨细胞或脂肪细胞分化尚不清楚。利用炭剥离胎牛血清（FBS）培养的小鼠克隆细胞系KS483，我们发现17β -雌二醇（E-2）以雌激素受体（ER）依赖的方式刺激祖细胞向成骨细胞的分化，同时抑制脂肪细胞的形成。E-2增加碱性磷酸盐（ALP）活性和结节形成，刺激核心结合因子α -1 （Cbfa1）、甲状旁腺激素/甲状旁腺激素相关蛋白受体（PTH/PTHrP-Rs）和骨钙素的信使RNA （mRNA）表达。相反，E-2减少脂肪细胞数量，下调过氧化物酶体增殖物激活受体- γ (pparγ)2、脂肪细胞蛋白2 （aP2）和脂蛋白脂肪酶（LPL） mRNA表达。此外，在异丁基甲基黄嘌呤、地塞米松和胰岛素的成脂混合物存在的情况下，E-2对成骨细胞和脂肪细胞分化的相互控制也被观察到。免疫组化染色显示，成骨细胞和脂肪细胞中均存在erα和erβ。发现了一种新的小鼠剪接变体ERbeta2，它与大鼠同种异构体有两个氨基酸残基不同。E-2下调erα、ERbeta1、ERbeta2 mRNA表达。E-2的作用并不局限于KS483细胞系，因为在小鼠骨髓细胞培养中也获得了类似的结果。我们的研究结果表明，雌激素，除了刺激成骨，抑制脂肪的形成，这可能解释了临床观察雌激素缺乏导致脂肪细胞增加。
Osteoblasts and adipocytes arise from a common progenitor cell in bone marrow. Whether estrogen directly regulates the progenitor cells differentiating into osteoblasts or adipocytes remains unknown. Using a mouse clonal cell line KS483 cultured in charcoal-stripped fetal bovine serum (FBS), we showed that 17beta-estradiol (E-2) stimulates the differentiation of progenitor cells into osteoblasts and concurrently inhibits adipocyte formation in an estrogen receptor (ER)-dependent way. E-2 increased alkaline phosphate (ALP) activity and nodule formation and stimulated messenger RNA (mRNA) expression of core-binding factor alpha-1 (Cbfa1), parathyroid hormone/parathyroid hormone-related protein receptors (PTH/PTHrP-Rs), and osteocalcin. In contrast, E-2 decreased adipocyte numbers and down-regulated mRNA expression of peroxisome proliferator-activated receptor-gamma (PPARgamma)2, adipocyte protein 2 (aP2), and lipoprotein lipase (LPL). Furthermore, the reciprocal control of osteoblast and adipocyte differentiation by E-2 was observed also in the presence of the adipogenic mixture of isobutylmethylxanthine, dexamethasone, and insulin. Immunohistochemical staining showed that ERalpha and ERbeta were present in osteoblasts and adipocytes. A new mouse splice variant ERbeta2 was identified, which differed in two amino acid residues from the rat isoform. E-2 down-regulated mRNA expression of ERalpha, ERbeta1, and ERbeta2. The effects of E-2 are not restricted to the KS483 cell line because similar results were obtained in mouse bone marrow cell cultures. Our results indicate that estrogen, in addition to stimulation of osteogenesis, inhibits adipogenesis, which might explain the clinical observations that estrogen-deficiency leads to an increase in adipocytes.