Col2-Cre and tamoxifen-inducible Col2-CreER target different cell populations in the knee joint.
Col2-Cre and tamoxifen-inducible Col2-CreER target different cell populations in the knee joint.
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DOI：
10.1016/j.joca.2015.07.025
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发表时间：
2016-01
影响因子：
7
通讯作者：
Olsen BR
中科院分区：
文献类型：
--
作者：
Nagao M;Cheong CW;Olsen BR
2型胶原(Col2)-Cre或他莫昔芬诱导的Col2- creer转基因小鼠系已被用于研究骨关节炎（OA）的细胞和分子发病机制。本研究的目的是探讨两种小鼠系的靶细胞是相同的还是不同的。我们将他莫昔芬诱导的Col2-CreER和Col2-Cre小鼠与Rosa tdTomato报告小鼠杂交，分析不同时间点的标记模式。在Col2-CreER小鼠中，在2周龄和2.5周龄给予他莫昔芬时，90.8%[95%可信区间（CI）（88.3, 93.2）]和82.8%(77.4,88.3)%的关节表面细胞呈番茄阳性，在注射后4.5个月仍有很强的活性。而在3周龄和4周龄给予他莫昔芬时，46.0%（32.8,59.1）和22.2 %（11.7,32.6）的表面细胞呈番茄阳性。当在8周龄时给予他莫昔芬时，观察到关节表面细胞中几乎没有番茄活性。在注射他莫昔芬的任何阶段，除关节软骨细胞外，生长板和骨骺均检测到番茄活性，内皮细胞中检测不到番茄活性，滑膜和韧带中检测不到番茄活性。Col2-Cre小鼠系的靶组织为关节软骨、生长板、半月板、内膜、韧带、骨和滑膜。本研究表明，可诱导的Col2-CreER小鼠的靶细胞模式与col2 - cree小鼠的靶细胞模式部分重叠，但不同于col2 - cree小鼠的靶细胞模式，其模式取决于给药时间。
Collagen type 2 (Col2)-Cre or tamoxifen-inducible Col2-CreER transgenic mouse lines have been used for studies to explore the cellular and molecular pathogenesis of osteoarthritis (OA). The purpose of this study is to investigate whether the targeted cells are the same or different in the two mouse lines. We crossed tamoxifen inducible Col2-CreER and Col2-Cre mice with Rosa tdTomato reporter mice and analyzed the labeling patterns at different time points. In the Col2-CreER mice, 90.8 [95% confidence interval (CI) (88.3, 93.2)] and 82.8 (77.4, 88.3) % of the articular surface cells are Tomato positive when tamoxifen was administered at 2 and 2.5 weeks of age and strong activity was observed even 4.5 months after injection. However, 46.0 (32.8, 59.1) and 22.2 (11.7, 32.6) % of the surface cells were Tomato positive when tamoxifen was administered at 3 and 4 weeks of age, respectively. Little to no Tomato activity in the articular surface cells was observed when tamoxifen was administered at 8 weeks of age. At any stage of tamoxifen injection, the Tomato activity was detected in growth plate and epiphyseal bone in addition to articular chondrocytes, but little in endothelium and not in the synovium and ligament. In contrast, the targeted tissues in the Col2-Cre mouse line were articular cartilage, growth plate, meniscus, endosteum, ligament, bone and synovium. This study demonstrates that the pattern of targeted cells in the inducible Col2-CreER mice are partially overlapping with but different from that of targeted cells in Col2-Cre mice and the pattern varies dependent on when tamoxifen is administered.