Role of collagen type II and perlecan in skeletal development
Role of collagen type II and perlecan in skeletal development
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DOI：
10.1111/j.1749-6632.2003.tb03217.x
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发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Fässler, R
中科院分区：
文献类型：
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作者：
Gustafsson, E;Aszódi, A;Fässler, R
软骨细胞外基质由致密的胶原蛋白网络组成，该胶原蛋白网络包裹了一系列其他对组织的正常形成和功能至关重要的特殊蛋白质。失去两种丰富的软骨成分，11型胶原和骨胶原，对骨骼发育有巨大的影响。11号胶原蛋白和Perlecan突变体都有严重的致死性软骨发育不良，其特征是生长板紊乱，缺乏胶原网络，软骨内骨形成缺陷，以及椎间盘发育异常。为了测试Perlecan缺失软骨中的胶原密度降低是否是由于胶原降解蛋白水解酶活性的增强，我们分析了突变组织中明胶酶的表达和活性。免疫组织化学分析显示，基质金属蛋白酶-9沉积有微弱但明显的扩张，进入Perlecan零生长板的肥大区。然而，原位和SDS-PAGE酶谱显示，在Perlecan缺失的软骨中，明胶酶(MMP2和MMP9)的活性没有改变，这表明它们主要与突变体中观察到的纤维网络减少无关。同样，在基质金属蛋白酶-9缺失的背景上交叉Perlecan突变体也不能挽救缺乏Perlecan的软骨的超微结构异常。
The cartilage extracellular matrix is composed of a dense collagen network that entraps a range of other specialized proteins important for the proper formation and function of the tissue. Loss of two abundant cartilage components, type 11 collagen and perlecan, has drastic effects on skeletal development. Both collagen 11 and perlecan mutants have severe and lethal chondrodysplasia characterized by disorganized growth plate, lack of collagen network, defective endochondral bone formation, and abnormal intervertebral disk development. To test whether the reduced collagen density in the perlecan-null cartilage is due to enhanced activity of collagen-degrading proteinases, we have analyzed gelatinase expression and activity in the mutant tissue. Immunohistochemical analysis revealed a weak, but clear, expansion of MMP-9 deposition into the hypertrophic zone of the perlecan-null growth plate. However, in situ and SDS-PAGE zymography showed that the activity of gelatinases (MMP-2 and MMP-9) is not altered in perlecan-null cartilage, suggesting that they are not primarily linked to the reduced fibrillar network observed in the mutant. Likewise, intercrossing of perlecan mutants onto an MMP-9-null background could not rescue the ultrastructural abnormalities of the perlecan-deficient cartilage.