Altered integration of matrilin-3 into cartilage extracellular matrix in the absence of collagen IX
Altered integration of matrilin-3 into cartilage extracellular matrix in the absence of collagen IX
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DOI：
10.1128/mcb.25.23.10465-10478.2005
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发表时间：
2005-12-01
影响因子：
5.3
通讯作者：
Grässel, S
中科院分区：
文献类型：
--
作者：
Budde, B;Blumbach, K;Grässel, S
matrilin是四种具有模块结构的非胶原寡聚细胞外基质蛋白的家族。Matrilin可以充当桥接不同大分子网络的适配器。因此，我们研究了胶原IX缺乏对matrilin-3整合到软骨组织中的影响。携带缺失的Col9a.1基因的小鼠缺乏功能性蛋白质的合成，并产生完全缺乏胶原IX的软骨原纤维。新生的胶原IX基因敲除小鼠表现出显着降低matrilin-3和软骨寡聚基质蛋白（COMP）的信号，特别是在软骨原基的椎体和肋骨。在不存在胶原IX的情况下，大量的matrilin-3被释放到培养的软骨细胞的培养基中，而不是如在野生型和COMP缺陷型细胞中那样被整合到细胞层中。在胶原IX不存在的情况下，matrilin-3的基因表达不受影响，但大大促进了从软骨中提取蛋白质。基质蛋白-3与含有胶原IX的软骨原纤维相互作用，而来自胶原IX敲除小鼠的原纤维缺乏基质蛋白-3，并且COMP缺陷的原纤维表现出中间整合。总之，基质蛋白-3整合到软骨原纤维中是通过与胶原IX的直接相互作用和与作为接头的COMP的间接相互作用发生的。Matrilin-3可以被认为是一种界面组分，能够互连大分子网络并介导软骨原纤维和原纤维外基质之间的相互作用。
The matrilins are a family of four noncollagenous oligomeric extracellular matrix proteins with a modular structure. Matrilins can act as adapters which bridge different macromolecular networks. We therefore investigated the effect of collagen IX deficiency on matrilin-3 integration into cartilage tissues. Mice harboring a deleted Col9a.1 gene lack synthesis of a functional protein and produce cartilage fibrils completely devoid of collagen IX. Newborn collagen IX knockout mice exhibited significantly decreased matrilin-3 and cartilage oligomeric matrix protein (COMP) signals, particularly in the cartilage primordium of vertebral bodies and ribs. In the absence of collagen IX, a substantial amount of matrilin-3 is released into the medium of cultured chondrocytes instead of being integrated into the cell layer as in wild-type and COMP-deficient cells. Gene expression of matrilin-3 is not affected in the absence of collagen IX, but protein extraction from cartilage is greatly facilitated. Matrilin-3 interacts with collagen IX-containing cartilage fibrils, while fibrils from collagen IX knockout mice lack matrilin-3, and COMP-deficient fibrils exhibit an intermediate integration. In summary, the integration of matrilin-3 into cartilage fibrils occurs both by a direct interaction with collagen IX and indirectly with COMP serving as an adapter. Matrilin-3 can be considered as an interface component, capable of interconnecting macromolecular networks and mediating interactions between cartilage fibrils and the extrafibrillar matrix.