Site-1 protease is essential for endochondral bone formation in mice.
Site-1 protease is essential for endochondral bone formation in mice.
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DOI：
10.1083/jcb.200708092
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发表时间：
2007-11-19
期刊：
影响因子：
--
通讯作者：
Sandell LJ
中科院分区：
文献类型：
--
作者：
Patra D;Xing X;Davies S;Bryan J;Franz C;Hunziker EB;Sandell LJ
位点-1蛋白酶（S1 P）在将潜伏的、膜结合的转录因子转化为它们的游离的、活性形式中具有重要功能。在哺乳动物中，S1 P在软骨细胞中的大量表达表明参与软骨细胞功能。为了确定S1 P在软骨和骨发育中的需求，我们建立了软骨特异性S1 P敲除小鼠（S1 Pcko）。S1 Pcko小鼠表现出软骨发育不良和完全缺乏软骨内骨化，即使Runx 2表达，印度刺猬信号，成骨细胞是完整的。然而，在S1 Pcko小鼠的软骨中，软骨细胞凋亡显著增加。从S1 Pcko软骨中提取的II型胶原蛋白基本上较低。在S1 Pcko小鼠中，胶原蛋白网络紊乱，胶原蛋白被捕获在软骨细胞中。超微结构分析表明，内质网（ER）在S1 Pcko软骨细胞是充血和破碎的方式严重的ER应力的特点。这些数据表明，S1 P活性是必要的一个专门的ER应力反应所需的软骨细胞的正常软骨的发生，从而endochondrialossification。
Site-1 protease (S1P) has an essential function in the conversion of latent, membrane-bound transcription factors to their free, active form. In mammals, abundant expression of S1P in chondrocytes suggests an involvement in chondrocyte function. To determine the requirement of S1P in cartilage and bone development, we have created cartilage-specific S1P knockout mice (S1Pcko). S1Pcko mice exhibit chondrodysplasia and a complete lack of endochondral ossification even though Runx2 expression, Indian hedgehog signaling, and osteoblastogenesis is intact. However, there is a substantial increase in chondrocyte apoptosis in the cartilage of S1Pcko mice. Extraction of type II collagen is substantially lower from S1Pcko cartilage. In S1Pcko mice, the collagen network is disorganized and collagen becomes entrapped in chondrocytes. Ultrastructural analysis reveals that the endoplasmic reticulum (ER) in S1Pcko chondrocytes is engorged and fragmented in a manner characteristic of severe ER stress. These data suggest that S1P activity is necessary for a specialized ER stress response required by chondrocytes for the genesis of normal cartilage and thus endochondral ossification.
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影响因子：
11.4
作者：
Lee, AH;Chu, GC;Glimcher, LH
通讯作者：
Glimcher, LH
DOI：
10.1111/j.1749-6632.2003.tb03217.x
发表时间：
2003-01-01
期刊：
TISSUE REMODELING
影响因子：
--
作者：
Gustafsson, E;Aszódi, A;Fässler, R
通讯作者：
Fässler, R
影响因子：
4.6
作者：
Hilton, MJ;Tu, XL;Long, FX
通讯作者：
Long, FX
影响因子：
64.8
作者：
Calfon, M;Zeng, HQ;Ron, D
通讯作者：
Ron, D
Osf2/Cbfa1：成骨细胞分化的转录激活因子
影响因子：
64.5
作者：
Ducy, P;Zhang, R;Karsenty, G
通讯作者：
Karsenty, G