Hypoxia-inducible factor regulation of ANK expression in nucleus pulposus cells: possible implications in controlling dystrophic mineralization in the intervertebral disc.
Hypoxia-inducible factor regulation of ANK expression in nucleus pulposus cells: possible implications in controlling dystrophic mineralization in the intervertebral disc.
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核细胞核细胞中ANK表达的低氧诱导因子调节：控制椎间盘中营养不良矿化的可能影响。
DOI：
10.1002/art.27558
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发表时间：
2010-09
影响因子：
--
通讯作者：
Risbud, Makarand V.
中科院分区：
文献类型：
--
作者：
Skubutyte, Renata;Markova, Dessislava;Freeman, Theresa A.;Anderson, D. Greg;Dion, Arnold S.;Williams, Charlene J.;Shapiro, Irving M.;Risbud, Makarand V.
Since nucleus pulposus cells reside in hypoxia, we determined if expression of ANK, a pyrophosphate transporter, is regulated by the HIF proteins. Quantitative RT-PCR and Western blot were used to measure ANK expression in nucleus pulposus cells. Transfections were performed to determine the effect of HIF-1/-2 on ANK promoter activity. ANK was expressed in embryonic and mature rat disc. Oxygen dependent changes in ANK expression in nucleus pulposus cells were minimal. However, silencing of HIF-1α and HIF-2α resulted in increased ANK expression and upregulation of promoter activity. HIF mediated suppression of ANK was validated by measuring promoter activity in HIF-1β null embryonic fibroblasts. Compared with wild type cells, in hypoxia, there was induction of promoter activity in the null cells. We overexpressed HIF-1α and HIF-2α in nucleus pulposus cells and noted a significant suppression in ANK promoter activity. Since the ANK promoter contains two hypoxia response elements (HRE), we performed site-directed mutagenesis and measured promoter activity. We found that HIF-1 can bind to either of the HRE and suppress promoter activity. In contrast, HIF-2 was required to bind to both HRE to suppress activity. Finally, analysis of human nucleus pulposus tissue showed that while ANK was expressed in normal tissue, there was increased expression of ANK along with alkaline phosphatase in the degenerate state. Both HIF-1 and HIF-2 serve as negative regulators of ANK expression in the disc. We propose that baseline ANK expression in the disc serves to prevent mineral formation under physiological conditions.
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影响因子：
--
作者：
Hirose, J;Ryan, LA;Masuda, I
通讯作者：
Masuda, I
影响因子：
6.2
作者：
Johnson, K;Goding, J;Terkeltaub, R
通讯作者：
Terkeltaub, R
影响因子：
3
作者：
Urban, JPG;Smith, S;Fairbank, JCT
通讯作者：
Fairbank, JCT
DOI：
10.3109/17453676908989540
发表时间：
1969-01-01
期刊：
ACTA ORTHOPAEDICA SCANDINAVICA
影响因子：
--
作者：
HASSLER, O
通讯作者：
HASSLER, O
影响因子：
--
作者：
Agrawal, Amit;Gajghate, Sachin;Risbud, Makarand V.
通讯作者：
Risbud, Makarand V.