EGR1 在 BMP9 介导的成骨细胞分化中发挥重要作用，促进 SMAD1/5 的磷酸化。
EGR1 plays an important role in BMP9-mediated osteoblast differentiation by promoting SMAD1/5 phosphorylation.
机构信息
Department of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Japan.
Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Japan.
出版信息
FEBS Lett. 2022 Jul;596(13):1720-1732. doi: 10.1002/1873-3468.14407. Epub 2022 Jun 1.
Bone morphogenetic proteins (BMPs) are essential regulators of skeletal homeostasis, and BMP9 is the most potently osteogenic among them. Here, we found that BMP9 and BMP2 rapidly induced early growth response 1 (EGR1) protein expression in osteoblasts through MEK/ERK pathway-dependent transcriptional activation. Knock-down of EGR1 using siRNA significantly inhibited BMP9-induced matrix mineralization and osteogenic marker gene expression in osteoblasts. Knock-down of EGR1 significantly reduced SMAD1/5 phosphorylation and inhibited the expression of their transcriptional targets in osteoblasts stimulated by BMP9. In contrast, forced EGR1 overexpression in osteoblasts enhanced BMP9-mediated osteoblast differentiation and SMAD1/5 phosphorylation. An intracellular association between EGR1 and SMAD1/5 was identified using immunoprecipitation assays. These results indicated that EGR1 plays an important role in BMP9-stimulated osteoblast differentiation by enhancing SMAD1/5 phosphorylation.
骨形态发生蛋白（BMPs）是骨骼动态平衡的重要调节因子，其中 BMP9 的成骨能力最强。在这里，我们发现 BMP9 和 BMP2 通过 MEK/ERK 通路依赖性转录激活，快速诱导成骨细胞中早期生长反应因子 1（EGR1）蛋白表达。使用 siRNA 敲低 EGR1 可显著抑制成骨细胞中 BMP9 诱导的基质矿化和成骨标记基因表达。敲低 EGR1 可显著降低 BMP9 刺激的成骨细胞中 SMAD1/5 的磷酸化，并抑制其转录靶基因的表达。相反，在成骨细胞中强制过表达 EGR1 可增强 BMP9 介导的成骨细胞分化和 SMAD1/5 磷酸化。免疫沉淀实验鉴定了 EGR1 和 SMAD1/5 之间的细胞内关联。这些结果表明，EGR1 通过增强 SMAD1/5 的磷酸化，在 BMP9 刺激的成骨细胞分化中发挥重要作用。
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