转化生长因子-β在诱导向成骨细胞分化的C3H10T1/2细胞中对KC趋化因子的表达。

KC chemokine expression by TGF-beta in C3H10T1/2 cells induced towards osteoblasts.

作者信息

Bischoff D S, Zhu J H, Makhijani N S, Yamaguchi D T

机构信息

Research Service, VA GLAHS, Los Angeles, CA 90073, USA.

出版信息

Biochem Biophys Res Commun. 2005 Jan 14;326(2):364-70. doi: 10.1016/j.bbrc.2004.11.035.

DOI:10.1016/j.bbrc.2004.11.035

PMID:15582587

Abstract

The effects of TGF-beta on expression of the platelet-derived growth factor-induced KC protein were explored in mouse mesenchymal C3H10T1/2 and pre-osteoblastic MC3T3-E1 cells to identify a potential role for TGF-beta in expression of angiogenic cytokines during osteogenic differentiation. KC is a member of the CXC chemokine family with homology to human IL-8, a potent neutrophilic chemotactic cytokine. TGF-beta treatment results in increased KC mRNA and protein secretion in C3H10T1/2 induced towards the osteoblastic lineage with all-trans-retinoic acid. This is due to up-regulated transcription rather than enhanced mRNA stability. No induction of KC expression was seen in untreated C3H10T1/2 or MC3T3-E1 upon TGF-beta stimulation. Use of the translational inhibitor cycloheximide results in mRNA "superinduction" suggesting other factors are involved that normally function to down-regulate KC expression. TGF-beta-stimulated conditioned media were a potent chemostimulant for human microvascular endothelial cells (HMEC-1). This activity could be inhibited by pre-incubation with anti-KC neutralizing antibodies.

摘要

在小鼠间充质C3H10T1/2细胞和前成骨细胞MC3T3-E1细胞中，研究了转化生长因子-β（TGF-β）对血小板衍生生长因子诱导的KC蛋白表达的影响，以确定TGF-β在成骨分化过程中血管生成细胞因子表达中的潜在作用。KC是CXC趋化因子家族的成员，与人IL-8同源，IL-8是一种有效的嗜中性粒细胞趋化细胞因子。用全反式维甲酸诱导C3H10T1/2细胞向成骨细胞谱系分化，TGF-β处理可导致KC mRNA和蛋白分泌增加。这是由于转录上调而非mRNA稳定性增强所致。在TGF-β刺激下，未处理的C3H10T1/2细胞或MC3T3-E1细胞中未见KC表达的诱导。使用翻译抑制剂环己酰亚胺导致mRNA“超诱导”，表明还有其他因素参与，这些因素通常起下调KC表达的作用。TGF-β刺激的条件培养基对人微血管内皮细胞（HMEC-1）是一种有效的化学刺激物。这种活性可通过与抗KC中和抗体预孵育来抑制。