The effects of retinoic acid on reversing the adipocyte differentiation into an osteoblastic tendency in ST2 cells, a murine bone marrow-derived stromal cell line
The effects of retinoic acid on reversing the adipocyte differentiation into an osteoblastic tendency in ST2 cells, a murine bone marrow-derived stromal cell line
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DOI：
10.1023/a:1014056012278
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发表时间：
2001-01-01
期刊：
影响因子：
2.2
通讯作者：
Nagai, K
中科院分区：
文献类型：
--
作者：
Ding, J;Woo, JT;Nagai, K
虽然小鼠骨髓基质细胞系ST 2已被证明可分化为成骨细胞，但该细胞向脂肪细胞的分化特征及其成脂和成骨之间的关系仍不清楚。由胰岛素、地塞米松（DEX）和3-异丁基-1-甲基黄嘌呤（IBMX）组成的成脂诱导培养基刺激了ST 2细胞中早期成脂标志物PPAR γ和晚期标志物GPDH的表达。RA抑制ST 2细胞诱导培养基中甘油三酯的积累和脂质染色水平，IC 50约为1 nM。诱导培养基中的过氧化物酶体增殖物激活受体γ和葡萄糖磷酸脱氢酶的表达上调也被RA抑制，而RA（30 nM）对细胞生长无影响。有趣的是，在RA存在的情况下，用诱导培养基处理细胞分别导致ALP活性比单独用RA或诱导培养基处理的细胞高3倍或10倍。RT-PCR分析表明，RA和诱导培养基的这种协同作用与抑制脂肪形成的过程一致。进一步的实验表明，IBMX在增加RA和ALP活性的效果中起关键作用。我们的研究结果表明，脂肪和成骨之间的关系，在ST 2细胞是间接相关的，脂肪形成的过程可能会逆转成成骨细胞的倾向。这是第一个报告表明，RA转化成成骨倾向成脂潜力。
Although the mouse bone marrow stromal cell line ST2 has been known to be differentiated into osteoblasts, the differentiation characteristics of the cell into adipocyte and the concerned relationship between its adipogenesis and osteogenesis remains unknown. The adipogenic induction medium which is made up of insulin, dexamethasone (DEX) and 3-isobutyl-1-methylxanthine (IBMX), stimulated the expression of n early adipogenic marker PPAR gamma and a late marker GPDH in ST2 cells. The triglyceride accumulation and lipid stain level generated by the induction medium in ST2 cells was inhibited by RA with IC50 at about 1 nM. The induction medium up-regulated expression of PPAR gamma and GPDH was also inhibited by RA whereas RA (30 nM) exterted no effect on the cell growth. Interestingly, treatment of the cells with induction medium in the presense of RA caused a 3- or 10-fold higher in ALP activity respectively as compared to those treated with RA or the induction medium alone. RT-PCR analysis showed that such a synergistic effect of RA and the induction medium paralleled the process of inhibition on adipogenesis. Additional experiments showed that IBMX played a key role in increasing the effect of RA and ALP activity. Our results suggested that the relationship between adipogenesis and osteogenesis in ST2 cells was reciprocally interrelated and the process of adipogenesis could be potentially reversed into an osteoblastogenic tendency. This is the first report demonstrating that RA transforms adipogenic potential into an osteoblastic tendency.