IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40975-7.html
   My bibliography  Save this article

CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications

Author

Listed:
  • Zhe Gong

    (Sir Run Run Shaw Hospital, Medical College of Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University)

  • Jinjin Zhu

    (Sir Run Run Shaw Hospital, Medical College of Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University)

  • Junxin Chen

    (Sir Run Run Shaw Hospital, Medical College of Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University)

  • Fan Feng

    (Obstetrics and Gynecology Hospital)

  • Haitao Zhang

    (Sir Run Run Shaw Hospital, Medical College of Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University)

  • Zheyuan Zhang

    (Sir Run Run Shaw Hospital, Medical College of Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University)

  • Chenxin Song

    (Sir Run Run Shaw Hospital, Medical College of Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University)

  • Kaiyu Liang

    (Sir Run Run Shaw Hospital, Medical College of Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University)

  • Shuhui Yang

    (Sir Run Run Shaw Hospital, Medical College of Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University)

  • Shunwu Fan

    (Sir Run Run Shaw Hospital, Medical College of Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University)

  • Xiangqian Fang

    (Sir Run Run Shaw Hospital, Medical College of Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University)

  • Shuying Shen

    (Sir Run Run Shaw Hospital, Medical College of Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University)

Abstract

Osteoarthritis is a prevalent age-related disease characterized by dysregulation of extracellular matrix metabolism, lipid metabolism, and upregulation of senescence-associated secretory phenotypes. Herein, we clarify that CircRREB1 is highly expressed in secondary generation chondrocytes and its deficiency can alleviate FASN related senescent phenotypes and osteoarthritis progression. CircRREB1 impedes proteasome-mediated degradation of FASN by inhibiting acetylation-mediated ubiquitination. Meanwhile, CircRREB1 induces RanBP2-mediated SUMOylation of FASN and enhances its protein stability. CircRREB1-FASN axis inhibits FGF18 and FGFR3 mediated PI3K-AKT signal transduction, then increased p21 expression. Intra-articular injection of adenovirus–CircRreb1 reverses the protective effects in CircRreb1 deficiency mice. Further therapeutic interventions could have beneficial effects in identifying CircRREB1 as a potential prognostic and therapeutic target for age-related OA.

Suggested Citation

  • Zhe Gong & Jinjin Zhu & Junxin Chen & Fan Feng & Haitao Zhang & Zheyuan Zhang & Chenxin Song & Kaiyu Liang & Shuhui Yang & Shunwu Fan & Xiangqian Fang & Shuying Shen, 2023. "CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40975-7
    DOI: 10.1038/s41467-023-40975-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40975-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-40975-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Botai Li & Lili Zhu & Chunlai Lu & Cun Wang & Hui Wang & Haojie Jin & Xuhui Ma & Zhuoan Cheng & Chengtao Yu & Siying Wang & Qiaozhu Zuo & Yangyang Zhou & Jun Wang & Chen Yang & Yuanyuan Lv & Liyan Jia, 2021. "circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Nick van Gastel & Steve Stegen & Guy Eelen & Sandra Schoors & Aurélie Carlier & Veerle W. Daniëls & Ninib Baryawno & Dariusz Przybylski & Maarten Depypere & Pieter-Jan Stiers & Dennis Lambrechts & Rie, 2020. "Lipid availability determines fate of skeletal progenitor cells via SOX9," Nature, Nature, vol. 579(7797), pages 111-117, March.
    3. Jinsoo Song & In-Jeoung Baek & Churl-Hong Chun & Eun-Jung Jin, 2018. "Dysregulation of the NUDT7-PGAM1 axis is responsible for chondrocyte death during osteoarthritis pathogenesis," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    4. Ying Qin & Qi Li & Wenbo Liang & Rongzhen Yan & Li Tong & Mutian Jia & Chunyuan Zhao & Wei Zhao, 2021. "TRIM28 SUMOylates and stabilizes NLRP3 to facilitate inflammasome activation," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    5. Dong-Hyun Kim & Sanghoon Kwon & Sangwon Byun & Zhen Xiao & Sean Park & Shwu-Yuan Wu & Cheng-Ming Chiang & Byron Kemper & Jongsook Kim Kemper, 2016. "Critical role of RanBP2-mediated SUMOylation of Small Heterodimer Partner in maintaining bile acid homeostasis," Nature Communications, Nature, vol. 7(1), pages 1-12, November.
    6. Manoj Arra & Gaurav Swarnkar & Ke Ke & Jesse E. Otero & Jun Ying & Xin Duan & Takashi Maruyama & Muhammad Farooq Rai & Regis J. O’Keefe & Gabriel Mbalaviele & Jie Shen & Yousef Abu-Amer, 2020. "LDHA-mediated ROS generation in chondrocytes is a potential therapeutic target for osteoarthritis," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    7. Benyu Liu & Buqing Ye & Xiaoxiao Zhu & Liuliu Yang & Huimu Li & Nian Liu & Pingping Zhu & Tiankun Lu & Luyun He & Yong Tian & Zusen Fan, 2020. "An inducible circular RNA circKcnt2 inhibits ILC3 activation to facilitate colitis resolution," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Chi Zhou & Wenxin Li & Zhenxing Liang & Xianrui Wu & Sijing Cheng & Jianhong Peng & Kaixuan Zeng & Weihao Li & Ping Lan & Xin Yang & Li Xiong & Ziwei Zeng & Xiaobin Zheng & Liang Huang & Wenhua Fan & , 2024. "Mutant KRAS-activated circATXN7 fosters tumor immunoescape by sensitizing tumor-specific T cells to activation-induced cell death," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Bin Li & Wen Xi & Ying Bai & Xue Liu & Yuan Zhang & Lu Li & Liang Bian & Chenchen Liu & Ying Tang & Ling Shen & Li Yang & Xiaochun Gu & Jian Xie & Zhongqiu Zhou & Yu Wang & Xiaoyu Yu & Jianhong Wang &, 2023. "FTO-dependent m6A modification of Plpp3 in circSCMH1-regulated vascular repair and functional recovery following stroke," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Wanying Wu & Jinyang Zhang & Xiaofei Cao & Zhengyi Cai & Fangqing Zhao, 2022. "Exploring the cellular landscape of circular RNAs using full-length single-cell RNA sequencing," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Kun Zhang & Pengfei Wang & Wei Huang & Shi-Hao Tang & Hanzhong Xue & Hao Wu & Ying Zhang & Yu Rong & Shan-Shan Dong & Jia-Bin Chen & Yan Zou & Ding Tian & Na Yang & Yifan Liang & Chungui Liu & Dongyan, 2024. "Integrated landscape of plasma metabolism and proteome of patients with post-traumatic deep vein thrombosis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Kosei Nagata & Hironori Hojo & Song Ho Chang & Hiroyuki Okada & Fumiko Yano & Ryota Chijimatsu & Yasunori Omata & Daisuke Mori & Yuma Makii & Manabu Kawata & Taizo Kaneko & Yasuhide Iwanaga & Hideki N, 2022. "Runx2 and Runx3 differentially regulate articular chondrocytes during surgically induced osteoarthritis development," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Wenjuan Zhang & Bowei Zhou & Xiao Yang & Jin Zhao & Jingjuan Hu & Yuqi Ding & Shuteng Zhan & Yifeng Yang & Jun Chen & Fu Zhang & Bingcheng Zhao & Fan Deng & Zebin Lin & Qishun Sun & Fangling Zhang & Z, 2023. "Exosomal circEZH2_005, an intestinal injury biomarker, alleviates intestinal ischemia/reperfusion injury by mediating Gprc5a signaling," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Tammy Liu & Gerd Melkus & Tim Ramsay & Adnan Sheikh & Odette Laneuville & Guy Trudel, 2023. "Bone marrow adiposity modulation after long duration spaceflight in astronauts," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Caojie Liu & Qiuchan Xiong & Qiwen Li & Weimin Lin & Shuang Jiang & Danting Zhang & Yuan Wang & Xiaobo Duan & Ping Gong & Ning Kang, 2022. "CHD7 regulates bone-fat balance by suppressing PPAR-γ signaling," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    9. Peng Wang & Zhitao Huang & Yili Peng & Hongwei Li & Tong Lin & Yingyu Zhao & Zheng Hu & Zhanmei Zhou & Weijie Zhou & Youhua Liu & Fan Fan Hou, 2022. "Circular RNA circBNC2 inhibits epithelial cell G2-M arrest to prevent fibrotic maladaptive repair," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    10. Zhenzhen Chen & Qiankun He & Tiankun Lu & Jiayi Wu & Gaoli Shi & Luyun He & Hong Zong & Benyu Liu & Pingping Zhu, 2023. "mcPGK1-dependent mitochondrial import of PGK1 promotes metabolic reprogramming and self-renewal of liver TICs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    11. Aaron Warren & Ryan M. Porter & Olivia Reyes-Castro & Md Mohsin Ali & Adriana Marques-Carvalho & Ha-Neui Kim & Landon B. Gatrell & Ernestina Schipani & Intawat Nookaew & Charles A. O’Brien & Roy Morel, 2023. "The NAD salvage pathway in mesenchymal cells is indispensable for skeletal development in mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Zehua Shang & Sitao Zhang & Jinrui Wang & Lili Zhou & Xinyue Zhang & Daniel D. Billadeau & Peiguo Yang & Lingqiang Zhang & Fangfang Zhou & Peng Bai & Da Jia, 2024. "TRIM25 predominately associates with anti-viral stress granules," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    13. Qilin Huang & Ziqiang Chu & Zihao Wang & Qiankun Li & Sheng Meng & Yao Lu & Kui Ma & Shengnan Cui & Wenzhi Hu & Wenhua Zhang & Qian Wei & Yanlin Qu & Haihong Li & Xiaobing Fu & Cuiping Zhang, 2024. "circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    14. Nian Liu & Jiacheng He & Dongdong Fan & Yang Gu & Jianyi Wang & Huimu Li & Xiaoxiao Zhu & Ying Du & Yong Tian & Benyu Liu & Zusen Fan, 2022. "Circular RNA circTmem241 drives group III innate lymphoid cell differentiation via initiation of Elk3 transcription," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40975-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.