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| 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 | Integration of ep- idemiology and animal neurotoxlcity data for risk assessment 显示文摘 | LI A A LEVINE T E BURNS C J | 2012 | Neurotoxieology2012，33，4： | 1 |
| 3 | Aspirin induction of apoptosis in esophageal cancer:a potential for chemoprevention 显示文摘 | Lotan R Levin B | 2000 | Cancer Epidemiol Biomarkers Prev2000，9，6： | 1 |
| 4 | Vitamin D and its analogues: do they protect against cardiovascular disease in patients with kidney disease 显示文摘 | Levin A Li YC | 2005 | Kidney Int2005，68，5： | 1 |
| 5 | Muhiple single nucleotide polymorphisms in the human urate transporter 1 (hURAT1) gene are associated with hyperuricemia in Han Chinese显示文摘 | LI C HAN L LEVIN A M | 2010 | J Med Genet2010，47，3： | 1 |
| 6 | Design of sel-assembled multifer- roic nanostructures in epitaxial films 显示文摘 | Levin I Li J Slutsker J | 2006 | Adv Mater2006，18，15： | 1 |
| 7 | Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis 显示文摘 | Munger KL Levin LI Hollis BW | 2006 | JAMA2006，296，23： | 1 |
| 8 | Design of self-assembled multiferroic nanostructures in epitaxial films显示文摘 | Levin I Li J H Slutsker J | | 0，，15： | 1 |
| 9 | Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis显示文摘 | Munger KL Levin LI Hollis BW | | 0，，： | 1 |
| 10 | Visual saliency based on scale space analysis in the frequency domain显示文摘 | LI J LEVINE M An X J | 2013 | IEEE Transactions Pattern Analysis and Machine Intelligence2013，35，4： | 1 |
| 11 | Visual saliency based on scale-space analysis in the frequency domain显示文摘 | Li J Levine M D An X etal | 2013 | Pattern Analysis and Machine Intelligence IEEE Transactions on2013，35，4： | 1 |
| 12 | Aging reduces neostriatal responsiveness to N-methyl-D-aspartate and dopamine:an in vitro electrophysiological study显示文摘 | Cepeda C Li Z Levine MS | 1996 | Neuroscience1996，73，3： | 1 |
| 13 | Multiple sclerosis and Epstein-Barr virus 显示文摘 | Levin LI Munger KL Rubertone MV | 2003 | JAMA2003，289，： | 1 |
| 14 | Aspirin induction of apoptosis in esophageal cancer:a potential for chemoprevention显示文摘 | Li M Lotan R Levin B | 2000 | Cancer Epidem Biomar2000，9，： | 1 |
| 15 | Multiple single nucleotide polymorphisms in the human urate transporter l(hURATl)gene are associated with hyperuricaemia in Han Chinese显示文摘 | Li C Han L Levin AM | 2010 | J Med Genet2010，47，3： | 1 |
| 16 | Bioresorbable vesi- cles formed through spontaneous self-assembly of amphiphilic po- ly(ethylene oxide)-block-polycaprolactone显示文摘 | Ghoroghchian P P Li G Z Levine D H | 2006 | Macromolecules2006，39，： | 1 |
| 17 | Multiple single nucleotide polymor- phisms in the human urate transporter 1 ( hURAT1 ) gene are asso- ciated with hyperuricaemia in Han Chinese 显示文摘 | Li C Han L Levin AM | 2010 | J Med Genet2010，47，3： | 1 |
| 18 | Temporal relationship between elevation of epstein-barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis显示文摘 | LEVIN LI MUNGER KL RUBERTONE MV | 2005 | JAMA2005，293，20： | 1 |
| 19 | Design of serf-assembled mulliferroic nanostruetures in epitaxial films显示文摘 | Levin I Li J Slutsker J | 2006 | Adv Mater2006，18，： | 1 |
| 20 | Mixed anxiety/de- pression symptoms in a large cancer cohort: prevalence by cancer type 显示文摘 | Brintzenhofe-Szoc KM Levin TT Li Y | 2009 | Psychosomatics2009，50，4： | 1 |
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