ATP induced brain-derived neurotrophic factor expression and release from osteoarthritis synovial fibroblasts is mediated by purinergic receptor P2X4.
ATP induced brain-derived neurotrophic factor expression and release from osteoarthritis synovial fibroblasts is mediated by purinergic receptor P2X4.
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DOI：
10.1371/journal.pone.0036693
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Sprott H
中科院分区：
文献类型：
--
作者：
Klein K;Aeschlimann A;Jordan S;Gay R;Gay S;Sprott H
脑源性神经营养因子(BDNF)是一种神经调节剂，参与中枢神经系统的伤害性超敏反应，在骨关节炎(OA)和类风湿关节炎(RA)患者的滑膜细胞中也有表达。我们研究了P2嘌呤受体在骨关节炎和类风湿关节炎患者滑膜成纤维细胞(SF)诱导BDNF表达中的作用。用嘌呤受体激动剂ATP、ADP或UTP刺激有症状的膝关节骨性关节炎和类风湿关节炎患者培养的SF。用TaqMan定量聚合酶链式反应检测脑源性神经营养因子mRNA的表达。用ELISA法检测细胞培养上清液中BDNF的释放。免疫组织化学方法检测滑膜组织中P2X4的表达。在ATP刺激前，siRNA可降低内源性P2X4的表达。在三磷酸腺苷刺激前，激酶通路被阻断。ATP刺激后2 h和5 h，OASF中BDNF mRNA表达水平明显升高。未刺激的OASF和RASF细胞培养上清液中BDNF的平均水平分别为19(±9)pg/ml和67(±49)pg/ml。三磷酸腺苷刺激后5h，SF上清液中BDNF水平才开始升高。P2X受体激动剂ATP和ADP均可诱导OASF中BDNF mRNA的表达，而P2Y嘌呤能受体激动剂UTP不能诱导OASF中BDNF的表达。通过siRNA介导的内源性P2X4水平降低，与杂乱对照相比，ATP诱导的OASF中BDNF mRNA的表达减少。抑制p38信号，而不是p44/42信号，降低了ATP介导的BDNF mRNA的诱导。在这里，我们展示了嘌呤能受体P2X4和p38激酶在ATP诱导的SF中神经营养因子BDNF的表达和释放中的功能作用。
Brain-derived neurotrophic factor (BDNF), a neuromodulator involved in nociceptive hypersensitivity in the central nervous system, is also expressed in synoviocytes of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. We investigated the role of P2 purinoreceptors in the induction of BDNF expression in synovial fibroblasts (SF) of OA and RA patients. Cultured SF from patients with symptomatic knee OA and RA were stimulated with purinoreceptor agonists ATP, ADP, or UTP. The expression of BDNF mRNA was measured by quantitative TaqMan PCR. BDNF release into cell culture supernatants was monitored by ELISA. P2X4 expression in synovial tissue was detected by immunohistochemistry. Endogenous P2X4 expression was decreased by siRNA transfection before ATP stimulation. Kinase pathways were blocked before ATP stimulation. BDNF mRNA expression levels in OASF were increased 2 h and 5 h after ATP stimulation. Mean BDNF levels in cell culture supernatants of unstimulated OASF and RASF were 19 (±9) and 67 (±49) pg/ml, respectively. BDNF levels in SF supernatants were only elevated 5 h after ATP stimulation. BDNF mRNA expression in OASF was induced both by P2X receptor agonists ATP and ADP, but not by UTP, an agonist of P2Y purinergic receptors. The ATP-induced BDNF mRNA expression in OASF was decreased by siRNA-mediated reduction of endogenous P2X4 levels compared to scrambled controls. Inhibition of p38, but not p44/42 signalling reduced the ATP-mediated BDNF mRNA induction. Here we show a functional role of the purinergic receptor P2X4 and p38 kinase in the ATP-induced expression and release of the neurotrophin BDNF in SF.
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影响因子：
3.4
作者：
Grimsholm, Ola;Rantapaa-Dahlqvist, Solbritt;Forsgren, Sture
通讯作者：
Forsgren, Sture
影响因子：
1.7
作者：
Oddiah, D;Anand, P;Rattray, M
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Rattray, M
影响因子：
15.3
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Kerschensteiner, M;Gallmeier, E;Behrens, L;Leal, V V;Misgeld, T;Klinkert, W E;Kolbeck, R;Hoppe, E;Oropeza-Wekerle, R L;Bartke, I;Stadelmann, C;Lassmann, H;Wekerle, H;Hohlfeld, R
通讯作者：
Hohlfeld, R
影响因子：
5.3
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Fukuoka, T;Kondo, E;Noguchi, K
通讯作者：
Noguchi, K
影响因子：
2.9
作者：
Hatami, Homeira;Oryan, Shahrbanoo;Ahmadiani, Abolhassan
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