|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Reduced EGFR signaling enhances cartilage destruction in a mouse osteoarthritis model显示文摘Osteoarthritis(OA) is a degenerative joint disease and a major cause of pain and disability in older adults. We have previously identified epidermal growth factor receptor(EGFR) signaling as an important regulator of cartilage matrix degradation during epiphyseal cartilage development. To study its function in OA progression, we performed surgical destabilization of the medial meniscus(DMM) to induce OA in two mouse models with reduced EGFR activity, one with genetic modification(EgfrWa5/1mice) and the other one with pharmacological inhibition(gefitinib treatment). Histological analyses and scoring at 3 months post-surgery revealed increased cartilage destruction and accelerated OA progression in both mouse models. TUNEL staining demonstrated that EGFR signaling protects chondrocytes from OA-induced apoptosis, which was further confirmed in primary chondrocyte culture. Immunohistochemistry showed increased aggrecan degradation in these mouse models, which coincides with elevated amounts of ADAMTS5 and matrix metalloproteinase 13(MMP13), the principle proteinases responsible for aggrecan degradation, in the articular cartilage after DMM surgery. Furthermore, hypoxia-inducible factor 2a(HIF2a), a critical catabolic transcription factor stimulating MMP13 expression during OA, was also upregulated in mice with reduced EGFR signaling. Taken together, our findings demonstrate a primarily protective role of EGFR during OA progression by regulating chondrocyte survival and cartilage degradation. | Xianrong Zhang Ji Zhu Fei Liu Yumei Li Abhishek Chandra L Scott Levin Frank Beier Motomi Enomoto-Iwamoto Ling Qin | 2014 | Bone Research2014，2，3： | 9 |
| 2 | JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis显示文摘 | SCOTT L M TONG W LEVINE R | 2007 | N Engl J Med2007，356，： | 1 |
| 3 | JAK2 exon 12 mutations in polycythemia vera and idiopathic eryth- rocytosis 显示文摘 | SCOTT L M TONG W LEVINE R L | 2007 | N Engl J ned2007，356，2： | 1 |
| 4 | JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis显示文摘 | SCOTT L M TONG W LEVINE R L | 2007 | N Engl J Med2007，356，： | 1 |
| 5 | JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis显示文摘 | SCOTT L M TONG W LEVINE R L | 2007 | N Engl J Med2007，356，： | 1 |
| 6 | Sural Flap Delay Procedure: A Preliminary Report显示文摘 | Detlev Erdmann Neil Gottlieb J Stewart Humphrey Trung C. Le William Bruno L Scott Levin | 2005 | Annals of Plastic Surgery2005，，5： | 1 |
| 7 | Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial显示文摘 | Guy L Clifton Alex Valadka David Zygun Christopher S Coffey Pamala Drever Sierra Fourwinds L Scott Janis Elizabeth Wilde Pauline Taylor Kathy Harshman Adam Conley Ava Puccio Harvey S Levin Stephen R McCauley Richard D Bucholz Kenneth R Smith John H Schmid | 2011 | Lancet Neurology2011，，2： | 1 |
| 8 | Warfarin dose assessment every 4 weeks versus every12 weeks in patients with stable international normalized ratios: arandomized trial 显示文摘 | SchulmanS Parpia S Stewart C Rudd -Scott L Julian J Levine M | 2011 | Ann Intern Med2011，155，10： | 1 |
| 9 | JAK2 exonl2 mutations in polycythemia vera and idiopathic erythrocytosis 显示文摘 | Scott L M Tong W Levine R L | 2007 | N Eng J Med2007，356，： | 1 |
| 10 | JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis显示文摘 | SCOTT L M TONG W LEVINE R L | | 0，，05： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员