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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 | Chcnlical and cnzym~ltic translbmaations of nimesulide to GSH conjugates through reductive and oxidative mechanisms显示文摘 | Zhou L Pang X Xie C el al | 2015 | Chem Res Toxicol2015，28，12： | 1 |
| 3 | is correlated with clinical progression and unfavorable prognosis in pancreatic cancer显示文摘 | Pang EJ Yang R Fu XB et aL Overexpression of long non -coding RNA MALATl | 2015 | Tumour Bioi2015，36，4： | 1 |
| 4 | Identification of peptide sequences that target to the brain using in vivo phage display 显示文摘 | Li Jingwei Zhang Qizhi Pang Zhiqing et aL | 2012 | Amino Acids2012，42，6： | 1 |
| 5 | Downregulation of metastasis suppressor genes in malignant phoechmmoeytoma显示文摘 | Ohta S Lai EW Pang AL | 2005 | Int J Cancer2005，114，1： | 1 |
| 6 | Postnatal malnutrition and growth retardation:an inevitable consequence of current recommendations in preterm infants? 显示文摘 | Embleton NE Pang N Cooke UJ el al | 2001 | Pediatrics2001，107，2： | 1 |
| 7 | In vitro antiviral activity of lute-in against hepatitis B virus 显示文摘 | Pang R Tao JY Zhang SL ef al | 2010 | Phyiother Res2010，24，11： | 1 |
| 8 | The analysis of related factorsof ventricular aneurysm formation in patients with acute myocar-dial infarction in northwest of China显示文摘 | Pang J Zhang Z Zheng TZ ef al | 2015 | lnt J Cardiol2015，15，1： | 1 |
| 9 | Alpba-lipoie acid ameliorales oxidative stress by increasing aldehyde dehydrogenase-2 activity in patients with acute coronary syndrome 显示文摘 | Li RJ Ji WQ Pang JJ el al | 2013 | Tohoku J Exp Med2013，229，1： | 1 |
| 10 | Design and synthesis of ther-mo-responsive hyperbranched poly( amine-ester) s as acid-sensitive drug carriers 显示文摘 | Pang Y Liu JY Su Y ef al | 2011 | Polym Chem2011，2，8： | 1 |
| 11 | Upregulation of dentin matrix protein 1promoter activities by core binding factor alpha1in human dental pulp stem cells显示文摘 | Pang J Zhang Y Ke J et al | 2007 | Biochem Biophys Res Commun2007，357，2： | 1 |
| 12 | Preparation and characterization of dual stimuli-responsive microcapsules with a supcrparamagnetic porous membrane and thermo-responsive gates显示文摘 | Yang W C Xie R Pang X Q ct al | 2008 | Journal of Membrane Science2008，321，： | 1 |
| 13 | Dissemination of supratentorial malignant gliomas via the cerehro-spinal fluid in children显示文摘 | Grabb PA Albright AL Pang D | 1992 | Neurosurgery1992，30，： | 1 |
| 14 | Down-regulation of metastasis suppressor genes in malignant pheochromocytoma显示文摘 | Ohta S Lai EW Pang AL | 2005 | Int J Cancer2005，114，1： | 1 |
| 15 | Downregulation of metastasis suppressor genes in malignant pheochromocytoma 显示文摘 | Ohta S Lai EW Pang AL | 2005 | Int J Cancer2005，114，1： | 1 |
| 16 | Inhibition of histone deacetylase activity attenuates renal fibroblast activation and in- terstitial fibrosis in obstructive nephropathy 显示文摘 | Pang M Kothapally J Mao H et al | 2009 | Am J Physiol Renal Physio12009，12，7： | 1 |
| 17 | Calcification in breast lesions: pathologists' perspective显示文摘 | Tse GM Tan PH Pang AL | 2008 | J Clin Pathol2008，61，2： | 1 |
| 18 | Calcification in breast lesions:pathologists' perspective显示文摘 | Tse GM Tan PH Pang AL | | 0，，02： | 1 |
| 19 | Small molecule antagonizes autoinhibition and activates AMP-activated protein kinase in cells显示文摘 | Pang T Zhang Z S Gu M el al | 2008 | J Biol Chem2008，283，16： | 1 |
| 20 | Evaluation and validation of Realtime reverse transcription-PCR assay using the Light Cycler system for the detection and quantitation of norovirus显示文摘 | Pang XL Lee B Chui L et al | 2004 | J Clin Microbiol2004，42，10： | 1 |
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