|
|
|
|
| 关节软骨细胞中β-连锁蛋白信号活化导致人β-连锁蛋白条件性活化小鼠的骨关节样表型 |
|
|
|
|
|
| Activation of β-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult β-catenin conditional activation mice |
|
|
|
|
|
| Zhu M., Tang D., Wu Q., Hao S., Chen M., Xie C., Rosier R.N., O'Keefe R.J., Zuscik M., Chen D. 2009/5/29 18:38:56 |
|
|
【发表评论】
|
|
|
|
|
打印|
推荐给好友
|
|
|
Journal of Bone and Mineral Research, 2009, Volume 24, Issue 1
|
|
|
|
|
|
|
| Osteoarthritis (OA) is a degenerative joint disease, and the mechanism of its pathogenesis is poorly understood. Recent human genetic association studies showed that mutations in the Frzb gene predispose patients to OA, suggesting that the Wnt/β-catenin signaling may be the key pathway to the development of OA. However, direct genetic evidence for β-catenin in this disease has not been reported. Because tissue-specific activation of the β-catenin gene (targeted by Col2a1-Cre) is embryonic lethal, we specifically activated the β-catenin gene in articular chondrocytes in adult mice by generating β-catenin conditional activation (cAct) mice through breeding of β-catenurfx(Ex3)/fx(Ex3) mice with Col2a1-CreERT2 transgenic mice. Deletion of exon 3 of the β-catenin gene results in the production of a stabilized fusion β-catenin protein that is resistant to phosphorylation by GSK-3β. In this study, tamoxifen was administered to the 3- and 6-mo-old Col2a1-CreERT2β--cateninfx(Ex3)/wt mice, and tissues were harvested for histologic analysis 2 mo after tamoxifen induction. Overexpression of β-catenin protein was detected by immunostaining in articular cartilage tissues of β-catenin cAct mice. In 5-mo-old β-catenin cAct mice, reduction of Safranin O and Alcian blue staining in articular cartilage tissue and reduced articular cartilage area were observed. In 8-mo-old β-catenin cAct mice, cell cloning, surface fibrillation, vertical clefting, and chondrophyte/osteophyte formation were observed. Complete loss of articular cartilage layers and the formation of new woven bone in the subchondral bone area were also found in β-catenin cAct mice. Expression of chondrocyte marker genes, such as aggrecan, Mmp-9, Mmp-13, Alp, Oc, and colX, was significantly increased (3- to 6-fold) in articular chondrocytes derived from β-catenin cAct mice. Bmp2 but not Bmp4 expression was also significantly upregulated (6-fold increase) in these cells. In addition, we also observed overexpression of β-catenin protein in the knee joint samples from patients with OA. These findings indicate that activation of β-catenin signaling in articular chondrocytes in adult mice leads to the premature chondrocyte differentiation and the development of an OA-like phenotype. This study provides direct and definitive evidence about the role of β-catenin in the development of OA. © 2009 American Society for Bone and Mineral Research. |
|
|
|
|
|
|
| Correspondence Address: Chen, D.; Department of Orthopaedics, University of Rochester, 601 Elmwood Avenue, Box 665, Rochester, NY 14642, United States; email: di_chen@uimc.rochester.edu |
|
|
|
|
|
|
|
|
|
|
|
请登录后发表评论，点击此处登录。
|
|
|
 疾病资源中心
摘自：《西氏内科学》，第23版
患者女性，21岁，因干咳、间歇性气促2个月到急诊科就诊。开始症状为上呼吸道感染引起的鼻塞、流涕和咳嗽。医生检查后开了抗生素。服药后鼻部症状缓解，但仍有轻微干咳和呼吸困难。其他症状包括疲劳和焦虑。否认发热、体重减轻、胸痛、端坐呼吸、气喘、鼻后滴漏、胃灼热以及神经系统症状。
医学数据库
|
