Inhibition of collagen fibrillogenesis by cells expressing soluble extracellular domains of DDR1 and DDR2.
Inhibition of collagen fibrillogenesis by cells expressing soluble extracellular domains of DDR1 and DDR2.
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DOI：
10.1016/j.jmb.2009.10.073
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发表时间：
2010-01-22
影响因子：
5.6
通讯作者：
Agarwal G
中科院分区：
文献类型：
--
作者：
Flynn LA;Blissett AR;Calomeni EP;Agarwal G
Collagen fiber assembly affects many physiological processes and is tightly controlled by collagen binding proteins. However to what extent membrane bound vs. cell secreted collagen binding proteins affect collagen fibrillogenesis is not well-understood. In our previous studies we had demonstrated that the membrane anchored extracellular domain (ECD) of the collagen receptor Discoidin Domain Receptor2 (DDR2) inhibits fibrillogenesis of collagen endogenously secreted by the cells. These results led to a novel functional role of the DDR2 ECD. However since soluble forms of DDR1 and DDR2 containing its extracellular domain (ECD) are known to naturally exist in the extracellular matrix, in this work we investigated if these soluble DDR ECDs may have a functional role in modulating collagen fibrillogenesis. For this purpose we created mouse osteoblast cell lines stably secreting DDR1 or DDR2 ECD as soluble proteins. Transmission electron microscopy, fluorescence microscopy, and hydroxyproline assays were used to demonstrate that DDR ECD expression reduced the rate and quantity of collagen deposition and induced significant changes in fiber morphology and matrix mineralization. Collectively, our studies advance our understanding of DDR receptors as powerful regulators of collagen deposition in the ECM and elucidate their multifaceted role in ECM remodeling.
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影响因子：
9.8
作者：
Bargal, Ruth;Cormier-Daire, Valerie;Raas-Rothschild, Annick
通讯作者：
Raas-Rothschild, Annick
影响因子：
4.8
作者：
Ikeda, K;Wang, LH;Lin, HC
通讯作者：
Lin, HC
影响因子：
5.6
作者：
Agarwal, Gunjan;Mihai, Cosmin;Iscru, Daniel F.
通讯作者：
Iscru, Daniel F.
影响因子：
7.5
作者：
Kadler KE;Hill A;Canty-Laird EG
通讯作者：
Canty-Laird EG
影响因子：
6
作者：
Ferri, N;Carragher, NO;Raines, EW
通讯作者：
Raines, EW