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Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway
Gang Zhong1,2, Ruiming Liang2, Jun Yao1
1Department of Orthopaedics Trauma and Hand Surgery & Guangxi Key Laboratory of Regenerative Medicine, International Joint Laboratory on Regeneration of Bone and Soft Tissue, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Background/Aims:
Current drug therapies for osteoarthritis (OA) are not practical because of the cytotoxicity and severe side-effects associated with most of them. Artemisinin (ART), an antimalarial agent, is well known for its safety and selectivity to kill injured cells. Based on its anti-inflammatory activity and role in the inhibition of OA-associated Wnt/β-catenin signaling pathway, which is crucial in the pathogenesis of OA, we hypothesized that ART might have an effect on OA.
Methods:
The chondro-protective and antiarthritic effects of ART on interleukin-1-beta (IL-1β)-induced and OA patient-derived chondrocytes were investigated in vitro using cell viability assay, glycosaminoglycan secretion, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blotting. We also used OA model rats constructed by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) in the joints to investigate the effects of ART on OA by gross observation, morphological staining, immunohistochemistry, and enzyme-linked immunosorbent assay.
Results:
ART exhibited potent anti-inflammatory effects by inhibiting the expression of proinflammatory chemokines and cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor alpha, and matrix metallopeptidase-13. It also showed favorable chondro-protective effect as evidenced by enhanced cell proliferation and viability, increased glycosaminoglycan deposition, prevention of chondrocyte apoptosis, and degeneration of cartilage. Further, ART inhibited OA progression and cartilage degradation via the Wnt/β-catenin signaling pathway, suggesting that it might serve as a Wnt/β-catenin antagonist to reduce inflammation and prevent cartilage degradation.
Conclusion:
In conclusion, ART alleviates IL-1β-mediated inflammatory response and OA progression by regulating the Wnt/β-catenin signaling pathway. Thereby, it might be developed as a potential therapeutic agent for OA.
Insights
Artemisinin (ART), an antimalarial drug, shows potential for treating osteoarthritis (OA) by reducing inflammation and protecting cartilage. ART effectively inhibits key inflammatory pathways and cartilage degradation, offering a promising new therapeutic avenue for OA patients.
Area of Science:
- Biomedical Science
- Pharmacology
- Rheumatology
Background:
- Current osteoarthritis (OA) treatments face limitations due to cytotoxicity and side effects.
- Artemisinin (ART), an antimalarial drug, is known for its safety and selective targeting of injured cells.
- ART's anti-inflammatory properties and its known inhibition of the OA-associated Wnt/β-catenin signaling pathway suggest therapeutic potential for OA.
Purpose of the Study:
- To investigate the chondro-protective and antiarthritic effects of Artemisinin (ART) in osteoarthritis.
- To explore ART's mechanism of action, particularly its influence on the Wnt/β-catenin signaling pathway in OA.
Main Methods:
- In vitro studies utilized IL-1β-induced and OA patient-derived chondrocytes to assess cell viability, glycosaminoglycan secretion, and gene/protein expression via immunofluorescence, qRT-PCR, and Western blotting.
- In vivo studies employed an OA rat model (ACLT+MMx) to evaluate ART's effects through gross observation, histological staining, immunohistochemistry, and ELISA.
Main Results:
- ART demonstrated significant anti-inflammatory effects by suppressing key cytokines (IL-1β, IL-6, TNF-α) and MMP-13.
- ART provided chondro-protection by enhancing chondrocyte viability, increasing glycosaminoglycan deposition, and preventing apoptosis and cartilage degeneration.
- ART inhibited OA progression and cartilage degradation, acting as a Wnt/β-catenin signaling antagonist.
Conclusions:
- Artemisinin (ART) effectively alleviates IL-1β-mediated inflammation and OA progression.
- ART regulates the Wnt/β-catenin signaling pathway, offering a novel mechanism for OA treatment.
- ART presents a potential therapeutic agent for osteoarthritis due to its anti-inflammatory and chondro-protective properties.
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