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首页> 外文期刊>Journal of Cellular Physiology >Spleen tyrosine kinase influences the early stages of multilineage differentiation of bone marrow stromal cell lines by regulating phospholipase C gamma activities
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Spleen tyrosine kinase influences the early stages of multilineage differentiation of bone marrow stromal cell lines by regulating phospholipase C gamma activities

机译：脾酪氨酸激酶影响早期阶段multilineage分化的骨髓通过调节磷脂酶C基质细胞系γ活动

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摘要

Bone marrow stromal cells (BMSCs) are multipotent cells that can differentiate into adipocytes and osteoblasts. Inadequate BMSC differentiation is occasionally implicated in chronic bone metabolic disorders. However, specific signaling pathways directing BMSC differentiation have not been elucidated. Here, we explored the roles of spleen tyrosine kinase (Syk) in BMSC differentiation into adipocytes and osteoblasts. We found that Syk phosphorylation was increased in the early stage, whereas its protein expression was gradually decreased during the adipogenic and osteogenic differentiation of two mouse mesenchymal stromal cell lines, ST2 and 10T(1/2), and a human BMSC line, UE6E‐7‐16. Syk inactivation with either a pharmacological inhibitor or Syk‐specific siRNA suppressed adipogenic differentiation, characterized by decreased lipid droplet appearance and the gene expression of fatty acid protein 4 ( Fabp4 ), peroxisome proliferator‐activated receptor γ2 (Pparg2) , CCAAT/enhancer binding proteins α (C/EBPα) , and C/EBPβ . In contrast, Syk inhibition promoted osteogenic differentiation, represented by increase in matrix mineralization and alkaline phosphatase (ALP) activity, as well as the expression levels of osteocalcin , runt‐related transcription factor 2 (Runx2) , and distal‐less homeobox 5 (Dlx5) mRNAs. We also found that Syk‐induced signals are mediated by phospholipase C γ1 (PLCγ1) in osteogenesis and PLCγ2 in adipogenesis. Notably, Syk‐activated PLCγ2 signaling was partly modulated through B‐cell linker protein (BLNK) in adipogenic differentiation. On the other hand, growth factor receptor‐binding protein 2 (Grb2) was involved in Syk‐PLCγ1 axis in osteogenic differentiation. Taken together, these results indicate that Syk‐PLCγ signaling has a dual role in regulating the initial stage of adipogenic and osteogenic differentiation of BMSCs.
机译：骨髓基质细胞(bmsc)是多功能的细胞,可以分化成脂肪细胞造骨细胞。偶尔涉及慢性骨代谢障碍。指挥BMSC分化没有阐明。酪氨酸激酶(麦克米兰BMSC分化脂肪细胞和成骨细胞。麦克米兰磷酸化是早期的增加阶段,而其蛋白表达在脂肪形成的和逐渐减少成骨分化的两个鼠标间充质基质细胞系,ST2和10 t (1/2)和一个人BMSC, UE6E 7检测16。失活与药理抑制剂或者麦克米兰特定核抑制脂肪形成的差异化特征降低脂滴外表和基因脂肪酸的表达蛋白4 (Fabp4),过氧物酶体扩散者优先激活受体γ2(Pparg2) CCAAT /增强器绑定蛋白α(C / EBPα)和C / EBPβ。抑制促进成骨分化,由矩阵增加矿化和碱性磷酸酶(ALP)活动骨钙素的表达水平,矮子应承担的相关转录因子2 (Runx2),和远端量少同源框5 (Dlx5) mrna。发现,麦克米兰感应信号是由磷脂酶Cγ1 (PLC)γ1)在骨生成和PLC在脂肪生成γ2。PLCγ2部分调制信号通过B细胞链接器(BLNK)在脂肪形成的蛋白质分化。受体结合蛋白2 (Grb2)应承担的参与麦克米兰PLCγ1轴在成骨分化。综上所述,这些研究结果表明麦克米兰必经PLCγ在调节信号具有双重作用脂肪形成的初始阶段和成骨的bmsc的分化。

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