Dysfunction of collagen synthesis and secretion in chondrocytes induced by wisp3 mutation.
Dysfunction of collagen synthesis and secretion in chondrocytes induced by wisp3 mutation.
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Wisp3突变导致软骨细胞胶原蛋白合成和分泌功能障碍
DOI：
10.1155/2013/679763
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发表时间：
2013
影响因子：
2.8
通讯作者：
Zhou HD
中科院分区：
文献类型：
--
作者：
Wang M;Man XF;Liu YQ;Liao EY;Shen ZF;Luo XH;Guo LJ;Wu XP;Zhou HD
Wisp 3基因突变可导致迟发性脊椎骨骺发育不良伴进行性关节病（SRDT-PA），但其潜在机制尚不清楚。为了阐明这一机制，我们构建了野生型和突变型Wisp 3表达载体，并转染人软骨细胞系C-20/A4，检测了Wisp 3蛋白的亚细胞定位、细胞增殖、细胞凋亡和Wisp 3介导的基因表达，并通过14 C-脯氨酸掺入实验分析了转染后软骨细胞胶原分泌的动态变化。突变的Wisp 3蛋白增加了C-20/A4细胞的增殖活性，减少了凋亡，并在胞浆中异常聚集。II型胶原的表达也下调C-20/A4细胞转染突变Wisp 3。野生型Wisp 3转染增加了细胞内胶原含量和细胞外胶原分泌，而突变型Wisp 3转染细胞失去了这一功能，并且突变型Wisp 3转染细胞的胶原分泌高峰期延迟。因此，异常的蛋白质分布，细胞增殖，胶原合成，并在Wisp 3突变的软骨细胞分泌可能有助于SEDT-PA的发病机制。
Wisp3 gene mutation was shown to cause spondyloepiphyseal dysplasia tarda with progressive arthropathy (SRDT-PA), but the underlying mechanism is not clear. To clarify this mechanism, we constructed the wild and mutated Wisp3 expression vectors and transfected into human chondrocytes lines C-20/A4; Wisp3 proteins subcellular localization, cell proliferation, cell apoptosis, and Wisp3-mediated gene expression were determined, and dynamic secretion of collagen in transfected chondrocytes was analyzed by 14C-proline incorporation experiment. Mutated Wisp3 protein increased proliferation activity, decreased apoptosis of C-20/A4 cells, and aggregated abnormally in cytoplasm. Expression of collagen II was also downregulated in C-20/A4 cells transfected with mutated Wisp3. Wild type Wisp3 transfection increased intracellular collagen content and extracellular collagen secretion, but the mutated Wisp3 lost this function, and the peak phase of collagen secretion was delayed in mutated Wisp3 transfected cells. Thus abnormal protein distribution, cell proliferation, collagen synthesis, and secretion in Wisp3 mutated chondrocytes might contribute to the pathogenesis of SEDT-PA.
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影响因子：
2.7
作者：
Kleer, Celina G.;Zhang, Yanhong;Merajver, Sofia D.
通讯作者：
Merajver, Sofia D.
影响因子：
4.8
作者：
Katsumi, A;Tuley, EA;Sadler, JE
通讯作者：
Sadler, JE
DOI：
10.1073/pnas.96.3.869
发表时间：
1999-02-02
影响因子：
11.1
作者：
Perbal, B;Martinerie, C;Roizman, B
通讯作者：
Roizman, B
影响因子：
11.2
作者：
Pal A;Huang W;Li X;Toy KA;Nikolovska-Coleska Z;Kleer CG
通讯作者：
Kleer CG
影响因子：
15.9
作者：
GOLDRING, MB;BIRKHEAD, JR;APPERLEY, JF
通讯作者：
APPERLEY, JF