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| 1 | TBK1-medicated DRP1 phosphorylation orchestrates mitochondrial dynamics and autophagy activation in osteoarthritis显示文摘Mitochondrial dynamics,including mitochondrial fission and fusion,are critical for maintaining mitochondrial functions.Evidence shows that TANK-binding kinase 1(TBK1)regulates mitochondrial fusion and fission and then mitophagy.Since a previous study demonstrates a strong correlation between mitophagy and osteoarthritis(OA),we herein investigated the potential role of TBK1 in OA process and mitochondrial functions.We demonstrated a strong correlation between TBK1 and OA,evidenced by significantly downregulated expression of TBK1 in cartilage tissue samples of OA patients and in the chondrocytes of aged mice,as well as TNF-α-stimulated phosphorylation of TBK1 in primary mouse chondrocytes.TBK1 overexpression significantly attenuated TNF-α-induced apoptosis and abnormal mitochondrial function in primary mouse chondrocytes.Furthermore,TBK1 overexpression induced remodeling of mitochondrial morphology by directly phosphorylating dynamin-related protein 1(DRP1)at Ser637,abolishing the fission of DRP1 and preventing its fragmentation function.Moreover,TBK1 recruitment and DRP1 phosphorylation at Ser637 was necessary for engulfing damaged mitochondria by autophagosomal membranes during mitophagy.Moreover,we demonstrated that APMK/ULK1 signaling contributed to TBK1 activation.In OA mouse models established by surgical destabilization of the medial meniscus,intraarticular injection of lentivirus-TBK1 significantly ameliorated cartilage degradation via regulation of autophagy and alleviation of cell apoptosis.In conclusion,our results suggest that the TBK1/DRP1 pathway is involved in OA and pharmacological targeting of the TBK1-DRP1 cascade provides prospective therapeutic benefits for the treatment of OA. | Sun-li Hu Abdullah Al Mamun Jian Shaw Sun-long Li Yi-feng Shi Xue-man Jin Ying-xin Yu Chao-zhi Pang Ze-yang Li Jia-jie Lu Yue-piao Cai Xiang-yang Wang Jian Xiao | 2023 | Acta Pharmacologica Sinica2023，44，3： | 2 |
| 2 | The sweet potato sporamin promoter confers high- level phytase expression and improves organic phosphorus acquisition and tuber yield of transgenic potato 显示文摘 | Hong YF Liu CY Cheng KJ Hour AL Chan MT Tseng TH Chert KY Shaw JF Yu SM | 2008 | Plant Mol Biol2008，67，： | 1 |
| 3 | Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9显示文摘 | Tan K Shaw AL Madsen B | 2003 | J Biol Chem2003，278，20： | 1 |
| 4 | Pregnancy amelioration of arthritis in SKG mice corresponds with alterations in serum amyloid A3 levels显示文摘 | Shaw LA Stefanski AL Peterson LK | 2012 | Am J Clin Exp Immunol2012，1，1： | 1 |
| 5 | A rapid method for the simultaneous determination of the major metabolites of sulphasalazine in plasma显示文摘 | Shaw PN Sivner AL Aarons L | 1983 | J Chromatogr1983，274，： | 1 |
| 6 | Prevalence of infeetion with herpes simplex virus types 1 and 2 in Australia:a nationwide population based survey显示文摘 | Cunningham AL Taylor R Taylor J Marks C Shaw J Mindel A | 2006 | Sex Transm Infect2006，82，3： | 1 |
| 7 | Large eddy simula- tion of windbreak flow 显示文摘 | Pattone E G Shaw R H Judd M J et al | 1998 | Boundary-Layer Meteorology1998，87，： | 1 |
| 8 | Linkingexperience* education, perception and earthquake preparedness显示文摘 | Rajib Shaw Koichi Shiwaku? Hirohide Kobayashi er al | 2004 | Disaster Prevention and Management2004，13，1： | 1 |
| 9 | Futureperspective of school disaster education in Nepal 显示文摘 | Koichi Shiwaku*Rajib Shaw Ram Chandra KandeheZ al | 2007 | DisasterPrevention and Management2007，16，57： | 1 |
| 10 | Risk factors forneural tube defects : associations between uncoupling pro-tein 2 polymorptfisms and spina显示文摘 | Volcik K A Shaw G M Zhu H el al | 2003 | Birth Defects ResA Clin Mol Teratol2003，67，3： | 1 |
| 11 | The role of oxidative stress in the prolonged inhibitory effect of ultrafine carbon black on epithelial cell function显示文摘 | Stone V Shaw J Brown DM et aL | 1998 | Toxicol Vitro1998，12，6： | 1 |
| 12 | A rapid method for the simuhaneous determination of the major metabolites of sulphasalazine in plasma显示文摘 | Shaw PN Sivner AL Aarons L | 1983 | J Chromatography1983，274，： | 1 |
| 13 | A rapid method for the simul- taneous determination of the major mctabolites of sulphasalazine in plasma 显示文摘 | Shaw PN Sivner AL Aarons L | 1983 | Chromatography1983，27，4： | 1 |
| 14 | Mercury mobility in unsaturated gold mine tailings, Murray Brook mine, New Brunswick, Canada 显示文摘 | SHAW S A AL T A MACQUARRIE K T B | 2006 | Applied Geochemistry2006，21，11： | 1 |
| 15 | Endothelin receptor antagonist SB209670 decreases lung allograft apoptosis and improves lung graft function after prolonged isehemia显示文摘 | Shaw MJ Shennib H Tayara L a al | 2000 | J Cardiovasc Pharmacol2000，36，51： | 1 |
| 16 | Vision loss in older persons 显示文摘 | Pelletier AL Thomas J Shaw FR | 2009 | Am Fam Physician2009，79，11： | 1 |
| 17 | A rapid method for the simultaneous determination of the major metabolites of sulphasalazine in plasma显示文摘 | Shaw PN Sivner AL Aarons L | 1983 | J Chromatography1983，274，： | 1 |
| 18 | The role of primary care in early detection and follow-up of cancer 显示文摘 | Emery JD Shaw K Williams B ct al | 2014 | Nat Rcv Clin Oncol2014，，： | 1 |
| 19 | Young children are more generous when others are aware of their actions 显示文摘 | Leimgruber KL Shaw A Santoset LR al | 2012 | Plos One2012，7，48： | 1 |
| 20 | Hyperphosphorylated neumfilament NF-H is a serum biomarker of axonal injury显示文摘 | Shaw G 'fang C Ellis 1L el al | 2005 | Biochem Biophys Res Commun2005，336，4： | 1 |
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