Enpp1 deficiency caused chondrocyte apoptosis by inhibiting AMPK signaling pathway
Journal of orthopaedic surgery and research(2023)
摘要
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.
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关键词
Enpp1,Osteoarthritis,Apoptosis,AMPK,AICAR
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