PDGF‑BB promotes the differentiation and proliferation of MC3T3‑E1 cells through the Src/JAK2 signaling pathway.

PDGF‑BB promotes the differentiation and proliferation of MC3T3‑E1 cells through the Src/JAK2 signaling pathway.
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PDGF-BB通过Src/JAK2信号通路促进MC3T3-E1细胞的分化和增殖

DOI:
10.3892/mmr.2018.9351
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发表时间:
2018-10
影响因子:
3.4
通讯作者:
Li Z
Li Z
中科院分区:
医学4区
文献类型:
--
作者:
Liu Q;Zhou Y;Li Z

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血小板源性生长因子-BB(PDGF-BB)在人成骨细胞的分化和增殖中起关键作用。Src和Janus激酶2(JAK 2)参与这些过程。我们前期的研究发现Src可以促进JAK 2的磷酸化。然而,尚未确定Src/JAK 2信号通路是否影响PDGF-BB介导的成骨细胞分化和增殖。本研究采用蛋白质印迹、聚合酶链反应、茜素红染色、碱性磷酸酶和细胞计数试剂盒-8等方法对这些问题进行了探讨。首先,证明PDGF-BB以时间依赖性方式激活MC 3 T3-E1细胞中的Src/JAK 2信号通路。此外,已证明PDGF-BB表达促进MC 3 T3-E1细胞分化和增殖;该过程被AG 1295、SU 6656和AG 490抑制,它们分别是PDGFR-β、Src和JAK 2的抑制剂。SU 6656下调Src和JAK 2的活性,而AG 490仅下调JAK 2的活性。因此,可以得出结论,Src是JAK 2的上游。PDGF-BB还上调了成骨相关基因的表达和矿物质结节的形成。然而,这些作用被SU 6656处理显著抑制。这表明PDGF-BB通过激活Src/JAK 2信号通路促进MC 3 T3-E1细胞的分化和增殖。这些结果提示PDGF-BB在骨质疏松和骨折的治疗中具有潜在的应用价值。
Platelet-derived growth factor-BB (PDGF-BB) serves a critical function in human osteoblast differentiation and proliferation. Src and Janus kinase 2 (JAK2) are involved in these processes. In our previous study, it was identified that Src could promote the phosphorylation of JAK2. However, it has yet to be determined whether the Src/JAK2 signaling pathway affects PDGF-BB-mediated osteoblast differentiation and proliferation. In the present study, western blotting, polymerase chain reaction, alizarin red staining, alkaline phosphatase and Cell Counting kit-8 were employed to explore these questions. Firstly, it was demonstrated that PDGF-BB activates the Src/JAK2 signaling pathway in MC3T3-E1 cells in a time-dependent manner. Furthermore, it was demonstrated that PDGF-BB expression promoted MC3T3-E1 cell differentiation and proliferation; this process was suppressed by AG1295, SU6656 and AG490, which are inhibitors of PDGFR-β, Src and JAK2, respectively. SU6656 downregulated the activity of Src and JAK2, while AG490 only downregulated JAK2 activity. Therefore, it was concluded that Src is upstream of JAK2. PDGF-BB also upregulated the expression of osteogenesis-associated genes, and the formation of mineral nodules. However, these effects were markedly inhibited by treatment with SU6656. This indicated that PDGF-BB promoted MC3T3-E1 cell differentiation and proliferation by activating the Src/JAK2 signaling pathway. These results suggested that PDGF-BB may have potential applications in the treatment of osteoporosis and bone fractures.
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