Physiological and pathological secretion of cartilage oligomeric matrix protein by cells in culture
Physiological and pathological secretion of cartilage oligomeric matrix protein by cells in culture
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DOI：
10.1074/jbc.273.41.26692
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发表时间：
1998-10-09
影响因子：
4.8
通讯作者：
Cohn, DH
中科院分区：
文献类型：
--
作者：
Délot, E;Brodie, SG;Cohn, DH
软骨寡聚基质蛋白（COMP）是软骨细胞外基质的五聚体结构蛋白，已在假性软骨发育不全和多发性骨骺发育不良（两种人类常染色体显性骨软骨发育不良）中发现异常。然而，该蛋白质的功能仍然未知。为了建立模型来研究 COMP 突变导致疾病的机制，我们分析了培养的软骨细胞、肌腱和韧带细胞中 COMP 的合成和分泌。在对照细胞内检测到的五聚蛋白表明五聚化是细胞内过程。患者细胞表达突变和正常 RNA，并分泌 COMP，其水平与对照相似，表明细胞外基质中可能发现异常五聚体。患者软骨内的内含物用抗 COMP 抗体染色，培养细胞呈现出类似的内含物，表明可能异常的 COMP 五聚体的分泌效率低于正常分子。我们得出的结论是，COMP 疾病可能是由于基质中 COMP 含量减少和软骨中存在异常五聚体导致的显性负面效应共同导致的。
Abnormalities in cartilage oligomeric matrix protein (COMP), a pentameric structural protein of the cartilage extracellular matrix, have been identified in pseudoachondroplasia and multiple epiphyseal dysplasia, two human autosomal dominant osteochondrodysplasias. However, the function of the protein remains unknown. With the goal of establishing a model to study the mechanisms by which COMP mutations cause disease, we have analyzed synthesis and secretion of COMP in cultured chondrocytes, tendon, and ligament cells. Pentameric protein detected inside of control cells suggested that pentamerization is an intracellular process. Patient cells expressed mutant and normal RNA and secreted COMP at levels similar to controls, suggesting that abnormal pentamers are likely to be found in the extracellular matrix. Inclusions within patient cartilage stained with anti-COMP antibodies, and cultured cells presented similar inclusions, indicating that presumably abnormal COMP pentamers are less efficiently secreted than normal molecules. We conclude that the COMP disorders are likely to result from a combination of a decreased amount of COMP in the matrix and a dominant negative effect due to the presence of abnormal pentamers in cartilage.