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丹参酮I抑制 IL-1β 诱导的细胞凋亡、炎症和软骨细胞 CHON-001 的细胞外基质降解,并缓解小鼠骨关节炎
Authors Wang X, Fan J, Ding X, Sun Y, Cui Z, Liu W
Received 21 May 2019
Accepted for publication 6 September 2019
Published 15 October 2019 Volume 2019:13 Pages 3559—3568
DOI https://doi.org/10.2147/DDDT.S216596
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 2
Editor who approved publication: Professor Jianbo Sun
Background: Osteoarthritis (OA) is a prevalent degenerative joint disease, which was characterized by inflammation and cartilage degradation. Accumulating evidence has demonstrated that Tanshinone I has an anti-inflammatory effect in various diseases. However, the efficacy of Tanshinone I as an anti-inflammatory agent in OA remains unclear. This study aimed to explore the role of Tanshinone I on OA both in vitro and in vivo.
Methods: CHON-001 cells were treated with IL-1β (10 ng/mL) for 72 hrs to induce OA model in vitro. Meanwhile, CHON-001 cells were pre-treated with 20 μM Tanshinone I for 24 hrs and then stimulated with IL-1β (10 ng/mL) for 72 hrs. CCK-8, immunofluorescence and flow cytometry assays were used to detect the viability, proliferation and apoptosis in CHON-001 cells, respectively. Western blotting assay was used to detect the levels of collagen II, aggrecan, MMP-13, cleaved caspase 1, Gasdermin D, SOX11 and p-NF-κB in CHON-001 cells. In addition, the mouse model of OA was built by anterior cruciate ligament transection (ACLT) in the right knee. Meanwhile, the mice were administrated with 10 or 30 mg/kg Tanshinone I for 8 weeks. Safranin-O/Fast Green staining was used to assess cartilage destruction in a mouse model of OA.
Results: In this study, IL-1β significantly induced apoptosis, extracellular matrix degradation and inflammatory response in CHON-001 cells. Tanshinone I significantly inhibited IL-1β-induced apoptosis in CHON-001 cells. In addition, the IL-1β-induced collagen II, aggrecan degradation, SOX11 downregulation, and MMP-13 and p-NF-κB upregulation in CHON-001 cells were notably reversed by Tanshinone I treatment. Moreover, Tanshinone I alleviated cartilage destruction and synovitis and reduced OARSI scores and subchondral bone thickness in a mouse model of OA.
Conclusion: Our findings showed that Tanshinone I could alleviate the progression of OA in vitro and in vivo. These results demonstrated that Tanshinone I might be regarded as a promising therapeutic agent for the treatment of OA.
Keywords: osteoarthritis, IL-1β, Tanshinone I, chondrocytes
