1. Academic Validation
  2. Enpp1 deficiency caused chondrocyte apoptosis by inhibiting AMPK signaling pathway

Enpp1 deficiency caused chondrocyte apoptosis by inhibiting AMPK signaling pathway

  • J Orthop Surg Res. 2023 Jun 27;18(1):462. doi: 10.1186/s13018-023-03923-1.
Zhiqiang Gao # 1 Qiang Wang # 1 Kai Guo # 1 Xinhua Li 2 Yufeng Huang 3
Affiliations

Affiliations

  • 1 Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University, 150 Jimo Rd, Shanghai, 200092, China.
  • 2 Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People's Republic of China. 1433747@tongji.edu.cn.
  • 3 Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University, 150 Jimo Rd, Shanghai, 200092, China. surgeonhng@alumni.tongji.edu.cn.
  • # Contributed equally.
Abstract

Objective and background: The deficiency of ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) causes the phenotype similar to knee osteoarthritis (OA). However, the molecular mechanism is poorly understood.

Method: The global deletion of Enpp1 (Enpp1-/-) mice was created to analyze the role of Enpp1 in the progress of knee OA. The Apoptosis, proliferation and chondrogenic differentiation ability of chondrocytes from wild-type (WT) and Enpp1-/- joints were compared. According to the results of high-throughput quantitative molecular measurements, the proteins of chondrocytes from WT and Enpp1-/- mice were used to explore the mechanism of Enpp1 deficiency-associated knee OA.

Result: In Enpp1-/- knee joints, we found significant chondrocyte Apoptosis and proteomic results showed that abnormal expression of AMP-activated protein kinase (AMPK) signaling pathway may contribute to this phenotype. In primary chondrocyte cultures in vitro, Enpp1 deletion dramatically enhancing chondrocyte Apoptosis. Meanwhile, we found Enpp1 deletion inhibits the phosphorylation of AMPK (P-AMPK). We also found that decreased level of P-AMPK and chondrocyte Apoptosis, which are caused by Enpp1 deficiency, can be reversed by Acadesine (AICAR), the activator of AMPK.

Conclusion: Consequently, Enpp1 deficiency plays an essential role in knee OA by regulating AMPK signaling pathway.

Keywords

AICAR; AMPK; Apoptosis; Enpp1; Osteoarthritis.

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