School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
Matrix Biol. 2009 Sep;28(7):416-24. doi: 10.1016/j.matbio.2009.07.001. Epub 2009 Jul 25.
The ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) family includes 19 secreted proteinases in man. ADAMTS16 is a recently cloned gene expressed at high levels in fetal lung and kidney and adult brain and ovary. The ADAMTS-16 protein currently has no known function. ADAMTS16 is also expressed in human cartilage and synovium where its expression is increased in tissues from osteoarthritis patients compared to normal tissues. In this study, we ascertained that the full length ADAMTS16 mRNA was expressed in chondrocytes and cloned the appropriate cDNA. Stable over-expression of ADAMTS16 in chondrosarcoma cells led to a decrease in cell proliferation and migration, though not adhesion, as well as a decrease in the expression of matrix metalloproteinase-13 (MMP13). The transcription start point of the human ADAMTS16 gene was experimentally identified as 138 bp upstream of the translation start ATG and the basal promoter was mapped out to -1802 bp. Overexpression of Egr1 induced ADAMTS16 promoter constructs of -157/+138 or longer whilst Sp1 induced all ADAMTS16 promoter constructs. Transforming growth factor beta (TGFbeta) stimulated expression of endogenous ADAMTS16 gene expression in chondrocyte cell lines.
ADAMTS（解整合素和金属蛋白酶域包含 19 个分泌蛋白水解酶在人）家族。ADAMTS16 是最近克隆的基因在胎儿肺和肾和成人脑和卵巢中高水平表达。ADAMTS-16 蛋白目前没有已知的功能。ADAMTS16 也在人软骨和滑膜中表达，其在骨关节炎患者的组织中表达增加，与正常组织相比。在这项研究中，我们确定全长 ADAMTS16 mRNA 在软骨细胞中表达，并克隆了相应的 cDNA。ADAMTS16 在软骨肉瘤细胞中的稳定过表达导致细胞增殖和迁移减少，但粘附没有减少，基质金属蛋白酶-13（MMP13）的表达减少。人类 ADAMTS16 基因的转录起始点实验确定为翻译起始 ATG 上游 138bp，基础启动子被映射到-1802bp。Egr1 的过表达诱导 -157/+138 或更长的 ADAMTS16 启动子构建体，而 Sp1 诱导所有 ADAMTS16 启动子构建体。转化生长因子β（TGFβ）刺激软骨细胞系中内源性 ADAMTS16 基因表达。
