Cystatin 10, a Novel Chondrocyte-specific Protein, May Promote the Last Steps of the Chondrocyte Differentiation Pathway*
Cystatin 10, a Novel Chondrocyte-specific Protein, May Promote the Last Steps of the Chondrocyte Differentiation Pathway*
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DOI：
10.1074/jbc.m211639200
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发表时间：
2003-11
影响因子：
4.8
通讯作者：
Y. Koshizuka;Takashi Yamada;K. Hoshi;T. Ogasawara;U. Chung;H. Kawano;Yusuke Nakamura;Kozo Nakamura;S. Ikegawa;H. Kawaguchi
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文献类型：
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作者：
Y. Koshizuka;Takashi Yamada;K. Hoshi;T. Ogasawara;U. Chung;H. Kawano;Yusuke Nakamura;Kozo Nakamura;S. Ikegawa;H. Kawaguchi
本研究试图表征胱抑素10 (Cst10)，我们最近发现它是一种与软骨内成骨有关的新蛋白。Cst10的表达是软骨特异性的，定位于小鼠生长板的增生性和增生性软骨细胞的细胞质中。在小鼠软骨细胞ATDC5中，Cst10的表达先于X型胶原的表达，并随着成熟同步增加。将转染Cst10 cDNA的ATDC5细胞与转染模拟载体的细胞进行比较，发现Cst10基因过表达促进了软骨细胞的增生性成熟和矿化，且X型胶原表达更早，茜素红染色更强。另一方面，作为软骨细胞早期分化标志的II型胶原表达和阿利新蓝染色在两种细胞中相似。Cst10基因的过表达还引起细胞核断裂、膜联蛋白V的出现、线粒体膜电位的改变和半胱天冬酶的激活。这些结果强烈提示Cst10可能在软骨细胞分化途径的最后步骤中发挥重要作用，作为成熟的诱导剂，随后是软骨细胞的凋亡。
This study attempts to characterize cystatin 10 (Cst10), which we recently identified as a novel protein implicated in endochondral ossification. Expression of Cst10 was specific to cartilage, localized in the cytosol of prehypertrophic and hypertrophic chondrocytes of the mouse growth plate. In the mouse chondrogenic cell line ATDC5, Cst10 expression preceded type X collagen expression and increased in synchrony with maturation. When we compared ATDC5 cells transfected with Cst10 cDNA with cells transfected with a mock vector, hypertrophic maturation and mineralization of chondrocytes were promoted by Cst10 gene overexpression in that type X collagen expression was observed earlier, and alizarin red staining was stronger. On the other hand, type II collagen expression and Alcian blue staining, both of which are markers of the early stage of chondrocyte differentiation, were similar in both cells. Overexpression of the Cst10 gene also caused fragmentation of nuclei, the appearance of annexin V, a change in the mitochondrial membrane potential, and activation of caspases. These results strongly suggest that Cst10 may play an important role in the last steps of the chondrocyte differentiation pathway as an inducer of maturation, followed by apoptosis of chondrocytes.