Matrix metalloproteinase-13 influences ERK signalling in articular rabbit chondrocytes.
Matrix metalloproteinase-13 influences ERK signalling in articular rabbit chondrocytes.
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基质金属蛋白酶 13 影响兔关节软骨细胞中的 ERK 信号传导。
DOI：
10.1016/j.joca.2006.01.006
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发表时间：
2006
影响因子：
7
通讯作者：
Partridge,NC
中科院分区：
文献类型：
--
作者：
Raggatt,LJ;JefcoatJr,SC;Choudhury,I;Williams,S;Tiku,M;Partridge,NC
基质金属蛋白酶-13（MMP-13）是一种细胞外MMP，其以高度特异性切割软骨的主要蛋白质组分II型胶原，并且与骨关节炎的病理学有关。本研究的目的是表征MMP-13在正常兔软骨细胞中的结合和内化动力学以及MMP-13是否影响细胞信号传导。方法用[125 I]-MMP-13结合试验研究MMP-13结合动力学，Western分析允许评估细胞内信号级联。特异性基因聚集蛋白聚糖和II型胶原蛋白。125 I-MMP-13与细胞的特异性结合在10 min后可检测到，2 h后达到平衡。[125 I]-MMP-13与软骨细胞的结合是特异性的，在75 nM时接近饱和。MMP-13的内化在20分钟后是明显的，在30分钟达到最大值，并在90分钟时恢复到基线。此外，受体相关蛋白（RAP）抑制MMP-13的内化，表明低密度脂蛋白受体相关蛋白-1（LRP 1）在这一过程中可能发挥作用。有趣的是，MMP-13的存在诱导了细胞外信号调节激酶1/2（ERK 1/2）蛋白的磷酸化，这表明响应于MMP-13被兔软骨细胞结合和内化，存在信号传导过程的启动。结论本研究证实了兔软骨细胞中存在MMP-13结合和内化系统，提示MMP-13可能通过该受体系统调节软骨细胞表型。
OBJECTIVEMatrix metalloproteinase-13 (MMP-13) is an extracellular MMP that cleaves type II collagen, the major protein component of cartilage, with high specificity and has been implicated in the pathology of osteoarthritis. The present study aimed to characterize the binding and internalization kinetics of MMP-13 in normal rabbit chondrocytes and whether MMP-13 affected cell signalling.METHODSRabbit chondrocytes were used in [125I]-MMP-13 binding assays to investigate the MMP-13 binding kinetics and Western analysis allowed for the assessment of intracellular signalling cascades.RESULTSRabbit chondrocytes were found to express the cartilage-specific genes aggrecan and type II collagen throughout their in vitro culture period. Appreciable specific cell-association of [125I]-MMP-13 was detected after 10min of exposure to the ligand and equilibrium was obtained after 2h. Binding of [125I]-MMP-13 to chondrocytes was specific and approached saturation at 75nM. Internalization of MMP-13 was evident after 20min, reached a maximum at 30min and had returned to baseline by 90min. Addition of receptor-associated protein (RAP) inhibited the internalization of MMP-13 indicating a likely role for low-density lipoprotein receptor-related protein-1 (LRP1) in this process. Interestingly the presence of MMP-13 induced phosphorylation of the extracellular signal-regulated kinase 1/2 (ERK1/2) protein showing that there is initiation of a signalling process in response to MMP-13 being bound and internalized by rabbit chondrocytes. However, this activation does not involve the MMP-13 internalization receptor LRP1.CONCLUSIONThese studies demonstrate and characterize the MMP-13 binding and internalization system in rabbit chondrocytes and indicate that MMP-13 may regulate the phenotype of the chondrocytes through this receptor system.
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影响因子：
15.9
作者：
Rohlmann, A;Gotthardt, M;Herz, J
通讯作者：
Herz, J
小鼠胶原酶 3 的重组催化结构域通过裂解其氨基肽来解聚 I 型胶原。
影响因子：
3.1
作者：
V. Lemaître;A. Jungbluth;Y. Eeckhout
通讯作者：
Y. Eeckhout
成骨细胞上间质胶原酶特异性受体的鉴定。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Omura,TH;Noguchi,A;Johanns,CA;Jeffrey,JJ;Partridge,NC
通讯作者：
Partridge,NC
DOI：
10.1016/s0021-9258(18)42072-8
发表时间：
1992-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Anders NykjaerSO;Claus M. Petersenl;Bjarne Mdllerl;Poul H. JensenS;MoestrupS;Thor L. Holtetll;Michael EtzerodtJI;Hans C. ThdgersenJJ;M. Munch;P. Andreasen;Jdrgen GliemannSO
通讯作者：
Anders NykjaerSO;Claus M. Petersenl;Bjarne Mdllerl;Poul H. JensenS;MoestrupS;Thor L. Holtetll;Michael EtzerodtJI;Hans C. ThdgersenJJ;M. Munch;P. Andreasen;Jdrgen GliemannSO
影响因子：
4.8
作者：
Bobick, BE;Kulyk, WM
通讯作者：
Kulyk, WM