Cyclic AMP signaling in bone marrow stromal cells has reciprocal effects on the ability of mesenchymal stem cells to differentiate into mature osteoblasts versus mature adipocytes.
Cyclic AMP signaling in bone marrow stromal cells has reciprocal effects on the ability of mesenchymal stem cells to differentiate into mature osteoblasts versus mature adipocytes.
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DOI：
10.1007/s12020-012-9717-9
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发表时间：
2012-12
期刊：
影响因子：
3.7
通讯作者：
Nissenson, Robert
中科院分区：
文献类型：
--
作者：
Kao, Richard;Lu, Weidar;Louie, Alyssa;Nissenson, Robert
关键词：
刺激性G蛋白介导的cAMP信号传导与骨骼稳态密切相关。然而，有限的信息是在调节间充质干细胞分化为成熟的成骨细胞和脂肪细胞的cAMP信号转导的作用。为了研究这一点，我们用毛喉素处理原代小鼠骨髓基质细胞（BMSCs）以刺激cAMP信号传导，并确定对成骨细胞和脂肪细胞分化的影响。暴露分化成骨细胞毛喉素显着抑制成骨细胞分化的晚期阶段的进展，这种效果是通过连续暴露于甲状旁腺素复制。令人惊讶的是，毛喉素激活BMSCs条件间充质干细胞（MSCs）的cAMP信号，经历增加的成骨分化和减少的成脂分化。PTH处理的BMSCs也增强了随后的成骨，但也促进了脂肪形成的增加。因此，cAMP信号传导的激活改变了MSC的谱系定向，有利于成骨，但以脂肪形成为代价。
Stimulatory G protein-mediated cAMP signaling is intimately involved in skeletal homeostasis. However, limited information is available on the role of the cAMP signaling in regulating the differentiation of mesenchymal stem cells into mature osteoblasts and adipocytes. To investigate this, we treated primary mouse bone marrow stromal cells (BMSCs) with forskolin to stimulate cAMP signaling and determined the effect on osteoblast and adipocyte differentiation. Exposure of differentiating osteoblasts to forskolin markedly inhibited progression to the late stages of osteoblast differentiation, and this effect was replicated by continuous exposure to PTH. Strikingly, forskolin activation of cAMP signaling in BMSCs conditioned mesenchymal stem cells (MSCs) to undergo increased osteogenic differentiation and decreased adipogenic differentiation. PTH treatment of BMSCs also enhanced subsequent osteogenesis, but promoted an increased adipogenesis as well. Thus, activation of cAMP signaling alters the lineage commitment of MSCs, favoring osteogenesis at the expense of adipogenesis.
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DOI：
10.1083/jcb.200610046
发表时间：
2007-02-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ge C;Xiao G;Jiang D;Franceschi RT
通讯作者：
Franceschi RT
影响因子：
6.2
作者：
ArmamentoVillareal, R;Ziambaras, K;Civitelli, R
通讯作者：
Civitelli, R
影响因子：
2.8
作者：
Alman, BA;Greel, DA;Wolfe, HJ
通讯作者：
Wolfe, HJ
影响因子：
64.5
作者：
Gong, YQ;Slee, RB;Warman, ML
通讯作者：
Warman, ML
影响因子：
4.8
作者：
Carroll, Shannon H.;Wigner, Nathan A.;Ravid, Katya
通讯作者：
Ravid, Katya