2. Academic Validation
  3. Compressive stress induces cartilage endplate degeneration through the Piezo1/YAP-TEAD/NLRP3 axis

Compressive stress induces cartilage endplate degeneration through the Piezo1/YAP-TEAD/NLRP3 axis

  • Life Sci. 2026 Mar 1:388:124195. doi: 10.1016/j.lfs.2026.124195.
Tong Cao 1,  Fushuai Peng 2,  Wei Wang 3,  Xingzhi Jing 1,  Fei Chen 2,  Mingtong Sun 4,  Jiaju Ma 1,  Wei Yang 5,  Zhihao Xu 1,  Zhenghao Xie 1,  Jun Dong 6,  Tao Li 7
Affiliations

Affiliations

  • 1 Department of Spine Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Weiqi Road, Huaiyin District, Jinan, Shandong, 250021, China.
  • 2 Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266071, China.
  • 3 Department of Pediatric Intensive Care Unit, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Road, Huaiyin District, Jinan, 250021, Shandong Province, China.
  • 4 Department of Emergency Surgery, Yidu Central Hospital of WeiFang City, WeiFang, Shan Dong, 262500, China.
  • 5 Department of Spinal Surgery, Pingdu People's Hospital, No.112 Yangzhou Road, Qingdao, Shandong, 266700, China.
  • 6 Department of Spine Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Weiqi Road, Huaiyin District, Jinan, Shandong, 250021, China. Electronic address: [email protected].
  • 7 Department of Spine Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Weiqi Road, Huaiyin District, Jinan, Shandong, 250021, China. Electronic address: [email protected].
PMID: 41506536 DOI: 10.1016/j.lfs.2026.124195
Abstract

Aims: To investigate the potential mechanisms by which compressive stress induces degeneration of cartilage endplate, and to elucidate the specific roles of mechanosensitive protein Piezo1, YAP, and NLRP3 in this process. A pressure-inflammation model of chondrocytes is proposed.

Materials and methods: Firstly, a bipedal standing mouse model was established to investigate the effect of mechanical stress on cartilage endplate degeneration and calcification. Next, cells were subjected to compression stress and western blot analysis as well as Bulk RNAseq were employed to detect the expression changes of Piezo1, YAP, NLRP3, ASC, and IL-1β. Additionally, intracellular CA2+ levels, Cytoskeleton and mitochondrial membrane potential were assessed. At last, Piezo1 chondrocyte conditional knockout mice were established to illustrate the role of Piezo1 in mechanical stress induced cartilage endplate degeneration.

Key findings: The bipedal standing mouse model demonstrated that compressive stress promotes cartilage endplate degeneration. The in vitro experiments demonstrated that compressive stress promoted degeneration of cartilage endplate via Piezo1-induced NLRP3 activation. Compressive stress activate Piezo1, triggering CA2+ influx and promoting cytoskeletal polymerization, which facilitated nuclear translocation of YAP. Subsequently, YAP-TEAD complex formation activated the NLRP3 inflammasome, leading to enhanced expression of IL-1β, MMP13, MMP3, RUNX2, and COL10, while suppressing expression of COL2 and SOX9.

Significance: Our study reveals the role of Piezo1/YAP-TEAD/NLRP3 axis in pressure stress-induced cartilage endplate degeneration. This signaling axis not only regulates inflammation, ossification, and oxidative stress responses in chondrocytes but also promotes chondrocyte Apoptosis through mitochondrial dysfunction. These findings provide novel molecular mechanisms for understanding the role of mechanical stress in cartilage degeneration.

Keywords

Compressive stress; Intervertebral disc degeneration; NLRP3; Piezo1; YAP.

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