Icariin alleviates osteoarthritis through PI3K/Akt/mTOR/ULK1 signaling pathway.

Abstract

OBJECTIVES:

This study aims to investigate the effects of Icariin (ICA) on interleukin-1β (IL-1β)-induced osteoarthritis (OA) and its potential mechanism of action.

METHODS:

SW1353 chondrocytes were pretreated with ICA for 2 h, followed by stimulation with IL-1β to mimic OA. Expression levels of matrix metalloproteinases (MMP-3) and collagen II were determined using real-time PCR and Western blot assays. Autophagy activation (by ICA) or inhibition (by shRNA) was determined based on the expression levels of ULK1, Beclin-1, LC3-II/I, and p62, using Western blot analysis. The phosphorylation levels of PI3K, Akt, mTOR, and ULK1 were also detected using Western blot analysis.

RESULTS:

IL-1β increased MMP-3 overproduction, induced collagen II degradation, and reduced the level of autophagy-associated proteins, including ULK1, Beclin-1, and LC3-II/I. In contrast, ICA pretreatment attenuated IL-1β-induced MMP-3 overproduction, increased collagen II expression, and induced expression of autophagy-related proteins. ICA also decreased PI3K, Akt, and mTOR phosphorylation, increased the production of ULK1, and induced autophagy. Short hairpin RNA-mediated knockdown of ULK1 led to activation of the PI3K/Akt/mTOR pathway, which reversed the protective effects of ICA.

CONCLUSIONS:

Our findings indicate that ICA can induce autophagy by regulating the PI3K/AKT/mTOR/ULK1 signaling pathway. This study suggests that ICA may be effective for treating OA.

• Authors: Yan Chen, Xiaoli Pan, Jing Zhao, Chunyan Li, Yupei Lin, Yu Wang, Xu Liu, Mei Tian
• Journal: European journal of medical research (Eur J Med Res) Vol. 27 Issue 1 Pg. 204 (Oct 17 2022) ISSN: 2047-783X [Electronic] England
• PMID: 36253872 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• Beclin-1
• Flavonoids
• Interleukin-1beta
• Intracellular Signaling Peptides and Proteins
• RNA, Small Interfering
• Collagen
• MTOR protein, human
• Autophagy-Related Protein-1 Homolog
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• ULK1 protein, human
• Matrix Metalloproteinase 3
• icariin

Topics

• Autophagy
• Autophagy-Related Protein-1 Homolog
• Beclin-1 (genetics, metabolism, pharmacology)
• Chondrocytes
• Collagen
• Flavonoids
• Humans
• Interleukin-1beta
• Intracellular Signaling Peptides and Proteins
• Matrix Metalloproteinase 3
• Osteoarthritis (drug therapy, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Small Interfering
• Signal Transduction
• TOR Serine-Threonine Kinases