Background Ossification of the posterior longitudinal ligament (OPLL) has a strong genetic background. Previous studies have shown that bone morphogenetic protein-2 (BMP2) and BMP2 mRNA are expressed in ossifying ...Background Ossification of the posterior longitudinal ligament (OPLL) has a strong genetic background. Previous studies have shown that bone morphogenetic protein-2 (BMP2) and BMP2 mRNA are expressed in ossifying matrix and chondrocytes adjacent to cartilaginous areas of OPLL tissues and mesenchymal cells with fibroblastic features in the immediate vicinity of the cartilaginous areas. It is suggested that BMP2 plays different roles in the different stages of development of OPLL. However, it remains unknown which factors induce ligament cells to produce BMP2. Methods OPLL patients (n=-192) and non-OPLL controls (n=304) were studied. Radiographs of the cervical spine were analyzed for extent of OPLL. We investigated whether single nucleotide polymorphisms of exons 3(-726) T/C and 3(-583) NG in the BMP2 gene are statistically associated with genetic susceptibility to OPLL in Chinese Han subjects. Results There was no statistical difference between the occurrence of exons 3(-726) T/C and 3(-583) NG and the occurrence of OPLL in the cervical spine. However, there was a significant association between occurrence of exon 3(-726) T/C polymorphism and occurrence of OPLL in males of cases and controls in the cervical spine. In addition, no significant association was found between the exons 3(-726) T/C and 3(-583) A/G with number of ossified cervical vertebrae in OPLL patients. Conclusions Exon 3(-583) A/G polymorphism in BMP2 gene is not associated with the occurrence and the extent of OPLL in the cervical spine. Chinese Han male patients with TC and CC genotypes in exon 3(-726) T/C have genetic susceptibility to OPLL but not to more extensive OPLL in the cervical spine.展开更多
本文旨在观察血管紧张素II (angiotensin II, Ang II)对血管平滑肌细胞核转录因子-κB (nuclear factor-κB, NF-κB)的活性及骨形成蛋白-2 (bone morphogenetic protein-2, BMP-2)表达的影响,以探讨Ang II参与动脉粥样硬化的机制,并探...本文旨在观察血管紧张素II (angiotensin II, Ang II)对血管平滑肌细胞核转录因子-κB (nuclear factor-κB, NF-κB)的活性及骨形成蛋白-2 (bone morphogenetic protein-2, BMP-2)表达的影响,以探讨Ang II参与动脉粥样硬化的机制,并探讨川芎嗪是否能抑制Ang II的促动脉粥样硬化作用。采用Western blot、免疫组化和原位杂交等方法分别检测Ang II刺激和川芎嗪干预后NF-κB活性、BMP-2 蛋白和 mRNA 表达的变化。结果显示:(1) Ang II 刺激激活 NF-κB。Ang II 刺激 15 min 即有 NF-κB p65核转移,30 min 达高峰(P<0.01),1 h 后减退。川芎嗪抑制 Ang II诱导的NF-κB激活,与Ang II组比较,川芎嗪 + Ang II组NF-κB活性显著降低 (P<0.01)。 (2) Ang II 刺激 6 h 时 BMP-2 表达增强(P<0.05),12 h 时减弱(P<0.01),24 h 时更弱(P<0.01)。川芎嗪 + Ang II组中,川芎嗪干预6 h 时BMP-2 表达亦增强,12 与24 h 时保持正常水平。 (3) 川芎嗪对正常细胞的NF-κB活性和BMP-2 表达无影响。以上结果表明,Ang II刺激后激活NF-κB并最终使生长抑制因子BMP-2 表达下降,这可能是其参与动脉粥样硬化发生的机制之一。BMP-2 一过性增高可能不依赖NF-κB通路的激活。川芎嗪可抑制Ang II诱导的NF-κB激活与 BMP-2 表达降低,提示它在抗动脉粥样硬化形成中起重要作用。展开更多
文摘Background Ossification of the posterior longitudinal ligament (OPLL) has a strong genetic background. Previous studies have shown that bone morphogenetic protein-2 (BMP2) and BMP2 mRNA are expressed in ossifying matrix and chondrocytes adjacent to cartilaginous areas of OPLL tissues and mesenchymal cells with fibroblastic features in the immediate vicinity of the cartilaginous areas. It is suggested that BMP2 plays different roles in the different stages of development of OPLL. However, it remains unknown which factors induce ligament cells to produce BMP2. Methods OPLL patients (n=-192) and non-OPLL controls (n=304) were studied. Radiographs of the cervical spine were analyzed for extent of OPLL. We investigated whether single nucleotide polymorphisms of exons 3(-726) T/C and 3(-583) NG in the BMP2 gene are statistically associated with genetic susceptibility to OPLL in Chinese Han subjects. Results There was no statistical difference between the occurrence of exons 3(-726) T/C and 3(-583) NG and the occurrence of OPLL in the cervical spine. However, there was a significant association between occurrence of exon 3(-726) T/C polymorphism and occurrence of OPLL in males of cases and controls in the cervical spine. In addition, no significant association was found between the exons 3(-726) T/C and 3(-583) A/G with number of ossified cervical vertebrae in OPLL patients. Conclusions Exon 3(-583) A/G polymorphism in BMP2 gene is not associated with the occurrence and the extent of OPLL in the cervical spine. Chinese Han male patients with TC and CC genotypes in exon 3(-726) T/C have genetic susceptibility to OPLL but not to more extensive OPLL in the cervical spine.
基金the National Natural Science Foundation of China (No. 30570725)
文摘本文旨在观察血管紧张素II (angiotensin II, Ang II)对血管平滑肌细胞核转录因子-κB (nuclear factor-κB, NF-κB)的活性及骨形成蛋白-2 (bone morphogenetic protein-2, BMP-2)表达的影响,以探讨Ang II参与动脉粥样硬化的机制,并探讨川芎嗪是否能抑制Ang II的促动脉粥样硬化作用。采用Western blot、免疫组化和原位杂交等方法分别检测Ang II刺激和川芎嗪干预后NF-κB活性、BMP-2 蛋白和 mRNA 表达的变化。结果显示:(1) Ang II 刺激激活 NF-κB。Ang II 刺激 15 min 即有 NF-κB p65核转移,30 min 达高峰(P<0.01),1 h 后减退。川芎嗪抑制 Ang II诱导的NF-κB激活,与Ang II组比较,川芎嗪 + Ang II组NF-κB活性显著降低 (P<0.01)。 (2) Ang II 刺激 6 h 时 BMP-2 表达增强(P<0.05),12 h 时减弱(P<0.01),24 h 时更弱(P<0.01)。川芎嗪 + Ang II组中,川芎嗪干预6 h 时BMP-2 表达亦增强,12 与24 h 时保持正常水平。 (3) 川芎嗪对正常细胞的NF-κB活性和BMP-2 表达无影响。以上结果表明,Ang II刺激后激活NF-κB并最终使生长抑制因子BMP-2 表达下降,这可能是其参与动脉粥样硬化发生的机制之一。BMP-2 一过性增高可能不依赖NF-κB通路的激活。川芎嗪可抑制Ang II诱导的NF-κB激活与 BMP-2 表达降低,提示它在抗动脉粥样硬化形成中起重要作用。