Notch is activated in RANKL-induced osteoclast differentiation and resorption
Notch is activated in RANKL-induced osteoclast differentiation and resorption
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DOI：
10.2741/3210
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发表时间：
2008-05-01
影响因子：
3.1
通讯作者：
Ren, Yijin
中科院分区：
文献类型：
--
作者：
Duan, Li;de Vos, Paul;Ren, Yijin
破骨细胞的分化和再吸收过程是由信号通路调控的，这一点有待进一步阐明。本研究的目的是探讨NF-κ B B和Notch在RANKL诱导的破骨细胞活性中的可能联系。为此，使用RANKL刺激小鼠破骨细胞前体细胞系RAW 264.7。计数多核TRAP（+）破骨细胞的数量并测量吸收面积。用EMSA法测定NF-κ B转录因子活性。RT-PCR和Western blotting分别检测Notch信号通路的主要靶点Hes 1 mRNA和蛋白表达。本研究检测了成熟的破骨细胞和骨吸收区域。在RANKL诱导的破骨细胞分化和吸收中，NF-κ B活性增加。RANKL刺激RAW 264. 7细胞后Hes 1 mRNA和蛋白表达上调。总之，NF-κ B信号介导RANKL诱导的破骨细胞分化和吸收，在此期间，Notch信号被激活。因此，Notch可能成为骨吸收相关疾病的一个新的治疗靶点。
The process of osteoclast differentiation and resorption is fine-tuned by signal pathways, which need to be further elucidated. The aim of this study was to explore the possible connections between NF-kappa B and Notch in RANKL-induced osteoclast activity. To this end, RANKL was used to stimulate mouse osteoclast precursor cell line RAW264.7. The number of multinucleated TRAP(+) osteoclasts was counted and the resorption area was measured. NF-kappa B transcriptional factor activity was determined by EMSA. Quantitative RT-PCR and Western blotting analysis were used to determine Hes1 (one of Notch signaling primary targets) mRNA and protein expressions respectively. Mature osteoclasts and bone resorption areas were detected in the present study. NF-kappa B activity was increased in RANKL-induced osteoclast differentiation and resorption. mRNA and protein expressions of Hes1 in RAW264.7 cells were up-regulated after RANKL stimulation. In conclusion, NF-kappa B signaling mediated RANKL-induced osteoclast differentiation and resorption, during which, Notch signaling was activated. Therefore, Notch could be a novel therapeutic target for bone resorption related diseases.