Brief report: stress-inducible nuclear protein 1 regulates matrix metalloproteinase 13 expression in human articular chondrocytes.
Brief report: stress-inducible nuclear protein 1 regulates matrix metalloproteinase 13 expression in human articular chondrocytes.
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DOI：
10.1002/art.38391
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发表时间：
2014-05
影响因子：
13.3
通讯作者：
Loeser, Richard F.
中科院分区：
文献类型：
--
作者：
Yammani, Raghunatha R.;Loeser, Richard F.
Nuclear protein-1 (nupr1) is a stress-inducible protein involved in gene transcription. The objectives of this study were to determine (a) if chondrocytes express nupr1 and (b) whether nupr1 regulates MMP-13 expression. Paraffin-embedded cartilage sections from normal human and osteoarthritic cartilage were immunostained using anti-nupr1 antibody. Total RNA to measure nupr1 expression was isolated from joint tissue obtained 8-weeks after surgery from young (12-week-old) and older (12-month-old) mice that underwent destabilization of medial meniscus (DMM) to induce osteoarthritis. Human chondrocytes were stimulated with 1-10ng/ml of IL-1β, 25-μM tert-butylhydroperoxide, or 2-μM of thapsigargin and nupr1 expression was analyzed by quantitative-PCR. In addition, chondrocytes were transfected with siRNA to knockdown nupr1 expression and then stimulated with IL-1β overnight. After incubation, the conditioned media was collected and analyzed for MMPs. Increased nupr1 immunostaining was noted in human osteoarthritic cartilage relative to normal cartilage. Expression was increased in mouse joint tissue from 12-month-old mice that underwent DMM surgery relative to sham controls. Stimulation of chondrocytes with IL-1β induced a 2-fold increase in nupr1 mRNA within 1hr and peaked to 4-fold at 6hrs. Treatment of chondrocytes with tert-butylhydroperoxide to induce oxidative stress, but not with thapsigargin to induce endoplasmic reticulum stress, increased nupr1 mRNA expression by over 2-fold. Knocking down nupr1 inhibited IL-1β-mediated induction of MMP-13. Nupr1 is expressed in cartilage, and its levels are increased in OA. Nupr1 expression is required for IL-1β-mediated expression of MMP-13. Thus, our study suggests a novel pathway for regulation of IL-1β-mediated production of MMPs in chondrocytes.
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影响因子：
4
作者：
Kurz, DJ;Decary, S;Erusalimsky, JD
通讯作者：
Erusalimsky, JD
ATF4是在体外和体内神经元中转录因子的氧化应激诱导的。
影响因子：
15.3
作者：
Lange, Philipp S.;Chavez, Juan C.;Pinto, John T.;Coppola, Giovanni;Sun, Chiao-Wang;Townes, Tim M.;Geschwind, Daniel H.;Ratan, Rajiv R.
通讯作者：
Ratan, Rajiv R.
影响因子：
--
作者：
Loeser, Richard F.;Olex, Amy L.;McNulty, Margaret A.;Carlson, Cathy S.;Callahan, Michael F.;Ferguson, Cristin M.;Chou, Jeff;Leng, Xiaoyan;Fetrow, Jacquelyn S.
通讯作者：
Fetrow, Jacquelyn S.
影响因子：
11.4
作者：
Goruppi, S;Bonventre, JV;Kyriakis, JM
通讯作者：
Kyriakis, JM
影响因子：
5.3
作者：
Goruppi, Sandro;Patten, Richard D.;Kyriakis, John M.
通讯作者：
Kyriakis, John M.