运行x2
基因沉默
间充质干细胞
生物
癌症研究
骨钙素
基因表达
发病机制
细胞生物学
分子生物学
碱性磷酸酶
基因
免疫学
遗传学
酶
生物化学
作者
Ituro Inoue,Ryuji Ikeda,S. Tsukahara
标识
DOI:10.1254/jphs.fmj05004x5
摘要
To understand the molecular pathogenesis of ossification of the posterior longitudinal ligament of the spine (OPLL), an ectopic bone formation disease, we performed cDNA microarray analysis on cultured ligament cells from OPLL patients to understand the molecular pathogenesis of OPLL. We identified promyelotic leukemia zinc finger (PLZF) as one of up-regulated genes and tumor necrosis factor-α-stimulated gene 6 (TSG-6) as one of down-regulated gene during osteoblastic differentiation. We investigated the roles of PLZF in the regulation of osteoblastic differentiation of human mesenchymal stem cells (hMSCs) and C2C12 cells. siRNA-mediated gene-silencing of PLZF resulted in a reduction of the expression of osteoblast-specific genes such as the alkaline phosphatase, collagen 1A1, Runx2/CBFA1, and osteocalcin genes in the presence of osteogenic differentiation medium (OS) in hMSCs. The overexpression of PLZF induced CBFA1 induction, suggesting that PLZF is an upstream regulator of CBFA1 and thereby participates in promoting the ossification of spinal ligament cells in OPLL patients. Adenoirus-mediated TSG-6 overexpression in hMSCs resulted in suppression of oseoblastic differentiation induced by either BMP-2 or OS. TSG-6 can bind to BMP-2 directly and thereby could inhibit BMP-2 signaling. Taken together, these findings indicate that PLZF and TSG-6 play important roles in early osteoblastic differentiation.
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