非综合征性矢状缝早闭患者原代成骨细胞中MAPK/ERK信号通路分析
MAPK/ERK Signaling Pathway Analysis in Primary Osteoblasts From Patients With Nonsyndromic Sagittal Craniosynostosis.
作者信息
Kim Sun-Don, Yagnik Garima, Cunningham Michael L, Kim Jinoh, Boyadjiev Simeon A
出版信息
Cleft Palate Craniofac J. 2014 Jan;51(1):115-9. doi: 10.1597/12-136. Epub 2013 Apr 8.
OBJECTIVE
The MAPK/ERK signaling pathway has been implicated in several craniosynostosis syndromes and represents a plausible target for therapeutic management of craniosynostosis. The causes of sagittal nonsyndromic craniosynostosis (sNSC) have not been well understood and the role that MAPK/ERK signaling cascade plays in this condition warrants an investigation. We hypothesized that MAPK-signaling is misregulated in calvarial osteoblasts derived from patients with sNSC.
METHODS
In order to analyze if the MAPK/ERK pathway is perturbed in sNSC, we established primary calvarial osteoblast cell lines from patients undergoing surgery for correction of this congenital anomaly. Appropriate negative and positive control cell lines were used for comparison, and we examined the levels of phosphorylated ERK by immunoblotting.
RESULTS
Primary osteoblasts from patients with sNSC showed no difference in ERK1/2 phosphorylation with or without FGF2 stimulation as compared with control osteoblasts.
CONCLUSION
Under the described test conditions, we did not observe convincing evidence that MAPK/ERK signaling contributes to the development of sNSC.
目的
丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）信号通路与多种颅缝早闭综合征有关，是颅缝早闭治疗管理的一个合理靶点。矢状缝非综合征性颅缝早闭（sNSC）的病因尚未完全明确，MAPK/ERK信号级联在这种情况下所起的作用值得研究。我们假设sNSC患者来源的颅骨成骨细胞中MAPK信号存在失调。
方法
为了分析sNSC中MAPK/ERK通路是否受到干扰，我们从接受该先天性异常矫正手术的患者中建立了原代颅骨成骨细胞系。使用适当的阴性和阳性对照细胞系进行比较，并通过免疫印迹检测磷酸化ERK的水平。
结果
与对照成骨细胞相比，sNSC患者的原代成骨细胞在有无FGF2刺激的情况下，ERK1/2磷酸化水平均无差异。
结论
在所描述的测试条件下，我们没有观察到令人信服的证据表明MAPK/ERK信号参与了sNSC的发生发展。
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