Adiponectin is a potential catabolic mediator in osteoarthritis cartilage.
Adiponectin is a potential catabolic mediator in osteoarthritis cartilage.
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DOI：
10.1186/ar3218
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发表时间：
2010
影响因子：
4.9
通讯作者：
Song YW
中科院分区：
文献类型：
--
作者：
Kang EH;Lee YJ;Kim TK;Chang CB;Chung JH;Shin K;Lee EY;Lee EB;Song YW
脂联素与骨关节炎（OA）的发病机制有关。我们研究了脂联素对OA软骨稳态的影响。免疫组化分析评价脂联素受体（AdipoRs）在OA软骨非病变区和病变区的差异表达。取原发性OA患者膝关节软骨和软骨细胞，在脂联素（0~30 μg/ml）存在下进行培养。检测条件培养液中总一氧化氮（NO）、基质金属蛋白酶（MMP）-1、-3、-13和金属蛋白酶组织抑制剂（TIMP）-1的水平。采用实时荧光定量逆转录聚合酶链反应（RT-PCR）检测诱导型一氧化氮合酶（iNOS）和基质金属蛋白酶（MMPs）的表达。在脂联素刺激的OA软骨外植体的上清液中测定胶原酶切割的II型胶原新表位（C1-2C）的浓度。在脂联素刺激的软骨细胞中评价激酶和NOS抑制剂的作用。AdipoR 1和AdipoR 2的表达水平在OA软骨的病变区显著高于非病变区。在非病变和病变区域之间，AdipoR 1阳性软骨细胞的增加率是AdipoR 2阳性软骨细胞的两倍。脂联素刺激OA软骨细胞显示增加总NO和MMP-1，-3，和-13水平相比，非刺激细胞。TIMP-1水平不受影响。脂联素可增加OA软骨培养物中C1-2C水平。AMP活化蛋白激酶（AMPK）和c-Jun N-末端激酶（JNK）抑制剂（化合物C和SP 600125）显著抑制脂联素诱导的总NO和MMP-1、-3和-13的产生。诱导型NOS抑制剂增强脂联素诱导的MMPs的表达。脂联素引起OA软骨基质降解，并通过AMPK和JNK途径增加人OA软骨细胞中MMP和iNOS的表达。脂联素的分解代谢作用可能被NO所抵消。
Adiponectin has been implicated in the pathogenesis of osteoarthritis (OA). We studied the effects of adiponectin on the OA cartilage homeostasis. Immunohistochemical analysis was performed to evaluate differential expression of adiponectin receptors (AdipoRs) in nonlesional and lesional areas of OA cartilage. Cartilage and chondrocytes from the knee joints of primary OA patients were cultured in the presence of adiponectin (0~30 μg/ml). The levels of total nitric oxide (NO), matrix metalloproteinase (MMP)-1, -3, and -13, and tissue inhibitor of metalloproteinase (TIMP)-1 were measured in the conditioned media. The levels of inducible NO synthase (iNOS) and MMPs were determined with the quantitative real-time reverse transcription-polymerase chain reaction. The concentrations of collagenase-cleaved type II collagen neoepitope (C1-2C) were determined in the supernatant of adiponectin-stimulated OA cartilage explants. The effects of kinase and NOS inhibitors were evaluated in the adiponectin-stimulated chondrocytes. The expression levels of both AdipoR1 and AdipoR2 were significantly higher in lesional than in nonlesional areas of OA cartilage. The increased rate of AdipoR1-positive chondrocytes was twice that of AdipoR2-positive chondrocytes when compared between nonlesional and lesional areas. Adiponectin-stimulated OA chondrocytes showed increased total NO and MMP-1, -3, and -13 levels compared with nonstimulated cells. The TIMP-1 level was not affected. The C1-2C levels were increased by adiponectin in OA cartilage explant culture. AMP-activated protein kinase (AMPK) and c-Jun N-terminal kinase (JNK) inhibitors (compound C and SP600125) significantly suppressed adiponectin-induced production of total NO and MMP-1, -3, and -13. Inducible NOS inhibitors enhanced the expression of the adiponectin-induced MMPs. Adiponectin causes matrix degradation in OA cartilage and increases MMPs and iNOS expression via the AMPK and JNK pathways in human OA chondrocytes. The catabolic effects of adiponectin may be counteracted by NO.
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影响因子：
5.8
作者：
Ho, LJ;Lin, LC;Tai, TY
通讯作者：
Tai, TY
影响因子：
4.1
作者：
Challa, T. Delessa;Rais, Y.;Ornan, E. Monsonego
通讯作者：
Ornan, E. Monsonego
影响因子：
4
作者：
Nishitani, Kohei;Ito, Hiromu;Nakamura, Takashi
通讯作者：
Nakamura, Takashi
影响因子：
3.9
作者：
Laurberg, Trine Bay;Frystyk, Jan;Stengaard-Pedersen, Kristian
通讯作者：
Stengaard-Pedersen, Kristian
DOI：
10.1006/bbrc.1995.1003
发表时间：
1995-01-05
影响因子：
3.1
作者：
MURRELL, GAC;JANG, D;WILLIAMS, RJ
通讯作者：
WILLIAMS, RJ