2. Academic Validation
  3. Curculigoside upregulates BMAL1 to decrease nucleus pulposus cell apoptosis by inhibiting the JAK/STAT3 pathway

Curculigoside upregulates BMAL1 to decrease nucleus pulposus cell apoptosis by inhibiting the JAK/STAT3 pathway

  • Osteoarthritis Cartilage. 2024 Nov 30:S1063-4584(24)01474-2. doi: 10.1016/j.joca.2024.11.009.
Linchuan Lei 1,  Hua Wang 2,  Zhuoyang Zhao 3,  Yuming Huang 4,  Xiaohui Huang 5,  Xingyu Guo 6,  Guowei Jiang 7,  Shunlun Chen 8,  Wantao Wang 9,  Xi Chen 10,  Zhaomin Zheng 11,  Jianru Wang 12,  Fan Chen 13
Affiliations

Affiliations

  • 1 Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Orthopedics and Traumatology, Guangzhou 510080, PR China; Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China. Electronic address: leilch3@mail2.sysu.edu.cn.
  • 2 Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Orthopedics and Traumatology, Guangzhou 510080, PR China. Electronic address: wangh227@mail.sysu.edu.cn.
  • 3 Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Orthopedics and Traumatology, Guangzhou 510080, PR China; Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China. Electronic address: zhaozhy27@mail2.sysu.edu.cn.
  • 4 Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Orthopedics and Traumatology, Guangzhou 510080, PR China. Electronic address: huangym73@mail2.sysu.edu.cn.
  • 5 Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China. Electronic address: hxhui@mail.sysu.edu.cn.
  • 6 Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Orthopedics and Traumatology, Guangzhou 510080, PR China; Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China. Electronic address: guoxy9@mail2.sysu.edu.cn.
  • 7 Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Orthopedics and Traumatology, Guangzhou 510080, PR China; Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China. Electronic address: jianggw3@mail2.sysu.edu.cn.
  • 8 Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Orthopedics and Traumatology, Guangzhou 510080, PR China. Electronic address: chenshlun3@mail2.sysu.edu.cn.
  • 9 Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Orthopedics and Traumatology, Guangzhou 510080, PR China. Electronic address: wangwt59@mail.sysu.edu.cn.
  • 10 Department of Pediatrics, The Second Xiangya Hospital, Central South Univeristy, Hunan 410011, PR China. Electronic address: chenxi6311@csu.edu.cn.
  • 11 Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Orthopedics and Traumatology, Guangzhou 510080, PR China; Pain Research Center, Sun Yat Sen University, PR China. Electronic address: zhzhaom@mail.sysu.edu.cn.
  • 12 Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Orthopedics and Traumatology, Guangzhou 510080, PR China. Electronic address: wangjru@mail.sysu.edu.cn.
  • 13 Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Orthopedics and Traumatology, Guangzhou 510080, PR China; Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China; Shenzhen Key Laboratory of Spine Surgery, Department of Spine Surgery, Peking University Shenzhen Hospital, Shenzhen, China. Electronic address: chenf273@mail.sysu.edu.cn.
PMID: 39622432 DOI: 10.1016/j.joca.2024.11.009
Abstract

Background: Intervertebral disc degeneration (IVDD) is a natural process that occurs with aging and is the main cause of low back pain. Basic helix-loop-helix ARNT-like 1 (BMAL1) plays key roles in the pathogenesis of many diseases. The present study investigates the role of curculigoside (CUR), which has been reported to be a potential anti-apoptotic compound in Other Diseases.

Methods: Dysregulated genes were identified by RNA Sequencing (RNA-seq). Western blotting (WB), immunohistochemistry, immunofluorescence (IF) staining, and real-time fluorescent quantitative polymerase chain reaction were used to detect BMAL1 expression in 25 human intervertebral disc specimens (male: female =13:12), tissues from BMAL1-knockout mice and from an IVDD mouse model. The regulatory effects of CUR and BMAL1 in nucleus pulposus (NP) cells after Small Interfering RNA (siRNA) transfection were examined by flow cytometry, IF staining and WB. The therapeutic effect of intraperitoneal CUR injection was also evaluated in mice.

Results: BMAL1 expression was negatively correlated with IVDD severity and was significantly lower in degenerative NP cells. After BMAL1 knockdown using siRNA, the Apoptosis rate of degenerative NP cells was significantly higher, while transfection with a lentivirus overexpressing BMAL1 exerted the opposite effect. Bioinformatics analysis revealed that BMAL1 is regulated by the JAK-STAT3 pathway, and CUR upregulated BMAL1 expression by inhibiting STAT3 phosphorylation, subsequently alleviating NP cell Apoptosis and increasing extracellular matrix (ECM) components., thus alleviating IVDD.

Conclusions: CUR can inhibit Apoptosis and improve the ECM by upregulating BMAL1 expression, which is reduced in IVDD. This study provides a therapeutic strategy to alleviate Apoptosis associated with inflammation-induced IVDD.

Keywords

Apoptosis; BMAL1; Curculigoside; Intervertebral disc degeneration.

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