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Open Access 01-12-2020 | Osteoarthrosis | Research article

Asiatic acid attenuates hypertrophic and fibrotic differentiation of articular chondrocytes via AMPK/PI3K/AKT signaling pathway

Authors: Na Liu, Dejie Fu, Junjun Yang, Pingju Liu, Xiongbo Song, Xin Wang, Rui Li, Zhenlan Fu, Jiajia Chen, Xiaoyuan Gong, Cheng Chen, Liu Yang

Published in: Arthritis Research & Therapy | Issue 1/2020

Abstract

Background

Osteoarthritis (OA), the most common joint disorder, is characterized by a progressive degradation of articular cartilage. Increasing evidence suggests that OA is closely associated with cartilage pathologies including chondrocyte hypertrophy and fibrosis.

Methods

In this study, we showed that asiatic acid (AA) treatment reduced chondrocyte hypertrophy and fibrosis. First, the cytotoxicity of AA (0, 5, 10, and 20 μM) to chondrocytes was evaluated, and 5 μM was selected for subsequent experiments. Then, we detected the gene and protein level of chondrocyte hypertrophic markers including type X collagen (COL-X), matrix metalloproteinase-13 (MMP-13), alkaline phosphatase (ALP), and runt-related transcription factor 2 (Runx2); chondrocyte fibrosis markers including type I collagen (COL-Ι) and alpha-smooth muscle actin (α-SMA); and chondrogenic markers including SRY-related HMG box 9 (SOX9), type II collagen (COL-II), and aggrecan (ACAN). Further, we tested the mechanism of AA on inhibiting chondrocyte hypertrophy and fibrosis. Finally, we verified the results in an anterior cruciate ligament transection (ACLT) rat OA model.

Results

We found that AA treatment inhibited the hypertrophic and fibrotic phenotype of chondrocytes, without affecting the chondrogenic phenotype. Moreover, we found that AA treatment activated AMP-activated protein kinase (AMPK) and inhibited phosphoinositide-3 kinase/protein kinase B (PI3K/AKT) signaling pathway in vitro. The results in an ACLT rat OA model also indicated that AA significantly attenuated chondrocyte hypertrophy and fibrosis.

Conclusion

AA treatment could reduce hypertrophic and fibrotic differentiation and maintain the chondrogenic phenotype of articular chondrocytes by targeting the AMPK/PI3K/AKT signaling pathway. Our study suggested that AA might be a prospective drug component that targets hypertrophic and fibrotic chondrocytes for OA treatment.

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Title: Asiatic acid attenuates hypertrophic and fibrotic differentiation of articular chondrocytes via AMPK/PI3K/AKT signaling pathway
Authors: Na Liu
Dejie Fu
Junjun Yang
Pingju Liu
Xiongbo Song
Xin Wang
Rui Li
Zhenlan Fu
Jiajia Chen
Xiaoyuan Gong
Cheng Chen
Liu Yang
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Osteoarthrosis
Osteoarthrosis
Published in: Arthritis Research & Therapy / Issue 1/2020
Electronic ISSN: 1478-6362
DOI: https://doi.org/10.1186/s13075-020-02193-0

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Abstract

Background

Methods

Results

Conclusion

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