NR4A1 promotes TNF-α-induced chondrocyte death and migration injury via activating the AMPK/Drp1/mitochondrial fission pathway
Identifieur interne : 000605 ( Main/Exploration ); précédent : 000604; suivant : 000606NR4A1 promotes TNF-α-induced chondrocyte death and migration injury via activating the AMPK/Drp1/mitochondrial fission pathway
Auteurs : Zhibo Zheng ; Shuai Xiang [République populaire de Chine] ; Yingjie Wang ; Yulei Dong ; Zeng Li ; Yongbo Xiang ; Yanyan Bian ; Bin Feng ; Bo Yang ; Xisheng WengSource :
- International Journal of Molecular Medicine [ 1107-3756 ] ; 2019.
Abstract
Nuclear receptor subfamily 4 group A member 1 (NR4A1)-induced chondrocyte death plays a critical role in the development of osteoarthritis through poorly defined mechanisms. The present study aimed to investigate the role of NR4A1 in regulating chondrocyte death in response to tumor necrosis factor-α (TNF-α) and cycloheximide (CHX) treatment, with a focus on mitochondrial fission and the AMP-activated protein kinase (AMPK) signaling pathway. The results demonstrated that NR4A1 was significantly upregulated in TNF-α and CHX exposed chondrocytes. Increased NR4A1 triggered mitochondrial fission via the AMPK/dynamin-related protein 1 (Drp1) pathway, resulting in mitochondrial dysfunction, and mitochondrial permeability transition pore (mPTP) opening-related cell death. Furthermore, excessive mitochondrial fission impaired chondrocyte migration through imbalance of F-actin homeo-stasis. Inhibiting NR4A1 attenuated TNF-α and CHX-induced mitochondrial fission and, thus, reduced mitochondrial dysfunction in chondrocytes, mPTP opening-related cell death and migration injury. Altogether, the present data confirmed that mitochondrial fission was involved in NR4A1-mediated chondrocyte injury via regulation of mitochondrial dysfunction, mPTP opening-induced cell death and F-actin-related migratory inhibition.
Url:
DOI: 10.3892/ijmm.2019.4398
PubMed: 31746366
PubMed Central: 6889925
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">NR4A1 promotes TNF-α-induced chondrocyte death and migration injury via activating the AMPK/Drp1/mitochondrial fission pathway</title><author><name sortKey="Zheng, Zhibo" sort="Zheng, Zhibo" uniqKey="Zheng Z" first="Zhibo" last="Zheng">Zhibo Zheng</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation><affiliation><nlm:aff id="af2-ijmm-45-01-0151">Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730</nlm:aff><wicri:noCountry code="subfield">Beijing 100730</wicri:noCountry></affiliation></author><author><name sortKey="Xiang, Shuai" sort="Xiang, Shuai" uniqKey="Xiang S" first="Shuai" last="Xiang">Shuai Xiang</name><affiliation wicri:level="1"><nlm:aff id="af3-ijmm-45-01-0151">Department of Orthopedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Orthopedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000</wicri:regionArea><wicri:noRegion>Shandong 266000</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Yingjie" sort="Wang, Yingjie" uniqKey="Wang Y" first="Yingjie" last="Wang">Yingjie Wang</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author><author><name sortKey="Dong, Yulei" sort="Dong, Yulei" uniqKey="Dong Y" first="Yulei" last="Dong">Yulei Dong</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author><author><name sortKey="Li, Zeng" sort="Li, Zeng" uniqKey="Li Z" first="Zeng" last="Li">Zeng Li</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author><author><name sortKey="Xiang, Yongbo" sort="Xiang, Yongbo" uniqKey="Xiang Y" first="Yongbo" last="Xiang">Yongbo Xiang</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author><author><name sortKey="Bian, Yanyan" sort="Bian, Yanyan" uniqKey="Bian Y" first="Yanyan" last="Bian">Yanyan Bian</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author><author><name sortKey="Feng, Bin" sort="Feng, Bin" uniqKey="Feng B" first="Bin" last="Feng">Bin Feng</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author><author><name sortKey="Yang, Bo" sort="Yang, Bo" uniqKey="Yang B" first="Bo" last="Yang">Bo Yang</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author><author><name sortKey="Weng, Xisheng" sort="Weng, Xisheng" uniqKey="Weng X" first="Xisheng" last="Weng">Xisheng Weng</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31746366</idno><idno type="pmc">6889925</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889925</idno><idno type="RBID">PMC:6889925</idno><idno type="doi">10.3892/ijmm.2019.4398</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000600</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000600</idno><idno type="wicri:Area/Pmc/Curation">000600</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000600</idno><idno type="wicri:Area/Pmc/Checkpoint">000556</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000556</idno><idno type="wicri:Area/Ncbi/Merge">000C26</idno><idno type="wicri:Area/Ncbi/Curation">000C26</idno><idno type="wicri:Area/Ncbi/Checkpoint">000C26</idno><idno type="wicri:doubleKey">1107-3756:2019:Zheng Z:nr:a:promotes</idno><idno type="wicri:Area/Main/Merge">000605</idno><idno type="wicri:Area/Main/Curation">000605</idno><idno type="wicri:Area/Main/Exploration">000605</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">NR4A1 promotes TNF-α-induced chondrocyte death and migration injury via activating the AMPK/Drp1/mitochondrial fission pathway</title><author><name sortKey="Zheng, Zhibo" sort="Zheng, Zhibo" uniqKey="Zheng Z" first="Zhibo" last="Zheng">Zhibo Zheng</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation><affiliation><nlm:aff id="af2-ijmm-45-01-0151">Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730</nlm:aff><wicri:noCountry code="subfield">Beijing 100730</wicri:noCountry></affiliation></author><author><name sortKey="Xiang, Shuai" sort="Xiang, Shuai" uniqKey="Xiang S" first="Shuai" last="Xiang">Shuai Xiang</name><affiliation wicri:level="1"><nlm:aff id="af3-ijmm-45-01-0151">Department of Orthopedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Orthopedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000</wicri:regionArea><wicri:noRegion>Shandong 266000</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Yingjie" sort="Wang, Yingjie" uniqKey="Wang Y" first="Yingjie" last="Wang">Yingjie Wang</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author><author><name sortKey="Dong, Yulei" sort="Dong, Yulei" uniqKey="Dong Y" first="Yulei" last="Dong">Yulei Dong</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author><author><name sortKey="Li, Zeng" sort="Li, Zeng" uniqKey="Li Z" first="Zeng" last="Li">Zeng Li</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author><author><name sortKey="Xiang, Yongbo" sort="Xiang, Yongbo" uniqKey="Xiang Y" first="Yongbo" last="Xiang">Yongbo Xiang</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author><author><name sortKey="Bian, Yanyan" sort="Bian, Yanyan" uniqKey="Bian Y" first="Yanyan" last="Bian">Yanyan Bian</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author><author><name sortKey="Feng, Bin" sort="Feng, Bin" uniqKey="Feng B" first="Bin" last="Feng">Bin Feng</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author><author><name sortKey="Yang, Bo" sort="Yang, Bo" uniqKey="Yang B" first="Bo" last="Yang">Bo Yang</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author><author><name sortKey="Weng, Xisheng" sort="Weng, Xisheng" uniqKey="Weng X" first="Xisheng" last="Weng">Xisheng Weng</name><affiliation><nlm:aff id="af1-ijmm-45-01-0151">Department of Orthopedic Surgery</nlm:aff></affiliation></author></analytic><series><title level="j">International Journal of Molecular Medicine</title><idno type="ISSN">1107-3756</idno><idno type="eISSN">1791-244X</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Nuclear receptor subfamily 4 group A member 1 (NR4A1)-induced chondrocyte death plays a critical role in the development of osteoarthritis through poorly defined mechanisms. The present study aimed to investigate the role of NR4A1 in regulating chondrocyte death in response to tumor necrosis factor-α (TNF-α) and cycloheximide (CHX) treatment, with a focus on mitochondrial fission and the AMP-activated protein kinase (AMPK) signaling pathway. The results demonstrated that NR4A1 was significantly upregulated in TNF-α and CHX exposed chondrocytes. Increased NR4A1 triggered mitochondrial fission via the AMPK/dynamin-related protein 1 (Drp1) pathway, resulting in mitochondrial dysfunction, and mitochondrial permeability transition pore (mPTP) opening-related cell death. Furthermore, excessive mitochondrial fission impaired chondrocyte migration through imbalance of F-actin homeo-stasis. Inhibiting NR4A1 attenuated TNF-α and CHX-induced mitochondrial fission and, thus, reduced mitochondrial dysfunction in chondrocytes, mPTP opening-related cell death and migration injury. Altogether, the present data confirmed that mitochondrial fission was involved in NR4A1-mediated chondrocyte injury via regulation of mitochondrial dysfunction, mPTP opening-induced cell death and F-actin-related migratory inhibition.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author><author><name sortKey="Lin, L" uniqKey="Lin L">L Lin</name></author><author><name sortKey="Zou, R" uniqKey="Zou R">R Zou</name></author><author><name sortKey="Wen, C" uniqKey="Wen C">C Wen</name></author><author><name sortKey="Wang, Z" uniqKey="Wang Z">Z Wang</name></author><author><name sortKey="Lin, F" uniqKey="Lin F">F Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Song E, K" uniqKey="Song E K">K Song E</name></author><author><name sortKey="Jeon, J" uniqKey="Jeon J">J Jeon</name></author><author><name sortKey="Jang, Dg" uniqKey="Jang D">DG 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Lee</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Bian, Yanyan" sort="Bian, Yanyan" uniqKey="Bian Y" first="Yanyan" last="Bian">Yanyan Bian</name><name sortKey="Dong, Yulei" sort="Dong, Yulei" uniqKey="Dong Y" first="Yulei" last="Dong">Yulei Dong</name><name sortKey="Feng, Bin" sort="Feng, Bin" uniqKey="Feng B" first="Bin" last="Feng">Bin Feng</name><name sortKey="Li, Zeng" sort="Li, Zeng" uniqKey="Li Z" first="Zeng" last="Li">Zeng Li</name><name sortKey="Wang, Yingjie" sort="Wang, Yingjie" uniqKey="Wang Y" first="Yingjie" last="Wang">Yingjie Wang</name><name sortKey="Weng, Xisheng" sort="Weng, Xisheng" uniqKey="Weng X" first="Xisheng" last="Weng">Xisheng Weng</name><name sortKey="Xiang, Yongbo" sort="Xiang, Yongbo" uniqKey="Xiang Y" first="Yongbo" last="Xiang">Yongbo Xiang</name><name sortKey="Yang, Bo" sort="Yang, Bo" uniqKey="Yang B" first="Bo" last="Yang">Bo Yang</name><name sortKey="Zheng, Zhibo" sort="Zheng, Zhibo" uniqKey="Zheng Z" first="Zhibo" last="Zheng">Zhibo Zheng</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Xiang, Shuai" sort="Xiang, Shuai" uniqKey="Xiang S" first="Shuai" last="Xiang">Shuai Xiang</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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