University of California, San Francisco, San Francisco, CA, USA.
Endocrine. 2012 Dec;42(3):622-36. doi: 10.1007/s12020-012-9717-9. Epub 2012 Jun 14.
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.
刺激性 G 蛋白介导的环磷酸腺苷信号通路与骨骼稳态密切相关。然而，关于环磷酸腺苷信号通路在调节间充质干细胞向成熟成骨细胞和脂肪细胞分化中的作用的信息有限。为了研究这一点，我们用 forskolin处理原代小鼠骨髓基质细胞（BMSCs）以刺激 cAMP 信号通路，并确定其对成骨细胞和脂肪细胞分化的影响。将分化中的成骨细胞暴露于 forskolin 中会明显抑制成骨细胞分化进入晚期阶段，而甲状旁腺激素（PTH）的持续暴露也能产生这种效果。令人惊讶的是，BMSCs 中的 cAMP 信号通路的 forskolin激活将间充质干细胞（MSCs）条件化，使其经历更多的成骨分化和更少的脂肪生成分化。PTH 处理 BMSCs 也增强了随后的成骨作用，但也促进了脂肪生成的增加。因此，cAMP 信号通路的激活改变了 MSC 的谱系决定，有利于成骨而不是脂肪生成。
