College of Pharmacy &Research Institute of Drug Development, Chonnam National University, Gwangju, Republic of Korea.
Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, South Korea.
Sci Rep. 2016 Oct 18;6:35655. doi: 10.1038/srep35655.
Osterix is a novel bone-related transcription factor involved in osteoblast differentiation, and bone maturation. Because a reciprocal relationship exists between adipocyte and osteoblast differentiation of bone marrow derived mesenchymal stem cells, we hypothesized that Osterix might have a role in adipogenesis. Ablation of Osterix enhanced adipogenesis in 3T3-L1 cells, whereas overexpression suppressed this process and inhibited the expression of adipogenic markers including CCAAT/enhancer-binding protein alpha (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ). Further studies indicated that Osterix significantly decreased PPARγ-induced transcriptional activity. Using co-immunoprecipitation and GST-pull down analysis, we found that Osterix directly interacts with PPARγ. The ligand-binding domain (LBD) of PPARγ was responsible for this interaction, which was followed by repression of PPARγ-induced transcriptional activity, even in the presence of rosiglitazone. Taken together, we identified the Osterix has an important regulatory role on PPARγ activity, which contributed to the mechanism of adipogenesis.
osterix 是一种新型的与骨相关的转录因子，参与成骨细胞分化和骨成熟。由于骨髓间充质干细胞的脂肪细胞和成骨细胞分化之间存在着一种相互关系，我们假设 osterix 可能在脂肪生成中起作用。osterix 的缺失增强了 3T3-L1 细胞的脂肪生成，而过表达则抑制了这一过程，并抑制了脂肪生成标志物包括 CCAAT/增强子结合蛋白 α（C/EBPα）和过氧化物酶体增殖物激活受体 γ（PPARγ）的表达。进一步的研究表明，osterix 显著降低了 PPARγ 诱导的转录活性。通过共免疫沉淀和 GST 下拉分析，我们发现 osterix 与 PPARγ 直接相互作用。PPARγ 的配体结合域（LBD）负责这种相互作用，随后抑制了 PPARγ 诱导的转录活性，即使在有罗格列酮的情况下也是如此。总之，我们确定了 osterix 对 PPARγ 活性有重要的调节作用，这有助于脂肪生成的机制。
