2. Academic Validation
  3. CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications

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

  • Nat Commun. 2023 Aug 28;14(1):5242. doi: 10.1038/s41467-023-40975-7.
Zhe Gong # 1,  Jinjin Zhu # 1,  Junxin Chen # 1,  Fan Feng # 2,  Haitao Zhang 1,  Zheyuan Zhang 1,  Chenxin Song 1,  Kaiyu Liang 1,  Shuhui Yang 1,  Shunwu Fan 3,  Xiangqian Fang 4,  Shuying Shen 5
Affiliations

Affiliations

  • 1 Department of Orthopaedic Surgery, 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, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China.
  • 2 Obstetrics and Gynecology Hospital, Kunpeng Road, Hangzhou, 310016, Zhejiang Province, China.
  • 3 Department of Orthopaedic Surgery, 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, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. 0099203@zju.edu.cn.
  • 4 Department of Orthopaedic Surgery, 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, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. orthofxq@zju.edu.cn.
  • 5 Department of Orthopaedic Surgery, 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, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. 11207057@zju.edu.cn.
  • # Contributed equally.
PMID: 37640697 DOI: 10.1038/s41467-023-40975-7
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.

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