Lee Hyun Woo, Kim Sang Yun, Kim A Young, Lee Eun Jig, Choi Je-Yong, Kim Jae Bum
School of Biological Sciences, Seoul National University, Seoul, Korea.
Stem Cells. 2009 Sep;27(9):2254-62. doi: 10.1002/stem.144.
In bone marrow, osteoblasts and adipocytes are differentiated from mesenchymal progenitor cells and their differentiation is reciprocally regulated by largely unknown mechanisms. In this study, we investigated downstream signaling cascades of adiponectin, a member of the adipocytokine family, in the regulation of osteoblast differentiation. Adiponectin augmented expression of several osteogenic marker genes and increased osteoblast differentiation in mesenchymal progenitor cells. The expression of cyclooxygenase-2 (COX2) was potently increased by adiponectin, whereas inhibition of COX2 activity abolished the effect of adiponectin on osteogenesis. In addition, adiponectin rapidly stimulated p38 mitogen-activated protein kinase via the adiponectin receptor, AdipoR1, which resulted in c-Jun activation for COX2 expression. Adiponectin also stimulated BMP2 expression in a COX2-dependent manner. Moreover, Runx2, a key osteogenic transcription factor, contributed to the acceleration of osteogenesis in the presence of adiponectin. Collectively, the finding that adiponectin could promote osteogenesis through an intracellular signaling cascade in mesenchymal progenitor cells suggests that adiponectin would be a potential therapeutic target for bone-related diseases.
在骨髓中，成骨细胞和脂肪细胞由间充质祖细胞分化而来，它们的分化受到很大程度上未知机制的相互调节。在本研究中，我们研究了脂肪细胞因子家族成员脂联素在成骨细胞分化调节中的下游信号级联反应。脂联素增强了几种成骨标记基因的表达，并增加了间充质祖细胞中的成骨细胞分化。脂联素能有效增加环氧合酶-2（COX2）的表达，而抑制COX2活性则消除了脂联素对成骨的作用。此外，脂联素通过脂联素受体AdipoR1快速刺激p38丝裂原活化蛋白激酶，从而导致c-Jun激活以促进COX2表达。脂联素还以COX2依赖的方式刺激骨形态发生蛋白2（BMP2）的表达。此外，关键的成骨转录因子Runx2在脂联素存在的情况下有助于加速成骨。总的来说，脂联素可通过间充质祖细胞中的细胞内信号级联促进成骨这一发现表明，脂联素可能是骨相关疾病的潜在治疗靶点。
