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Amentoflavone alleviated cartilage injury and inflammatory response of knee osteoarthritis through PTGS2

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Abstract

The role of amentoflavone on cartilage injury in knee osteoarthritis (KOA) rats and the underlying mechanism were explored. KOA rat and IL-1β-stimulated chondrocyte models were constructed. MTT, colony formation, and ELISA were performed to determine the cytotoxicity, cell proliferation, and inflammatory factors. The role of PTGS2 in IL-1β-stimulated chondrocytes was also confirmed through transfecting PTGS2 overexpression and silencing plasmids. Further, we analyzed how amentoflavone regulated PTGS2 to improve IL-1β-stimulated chondrocytes in vitro. Additionally, we analyzed the expression of PTGS2 after amentoflavone treatment. In vivo, HE and Safranin-O staining were carried out, and the inflammatory response was detected by ELISA and HE staining. In addition, we also analyzed the regulatory effect of amentoflavone on PTGS2 and explored the mechanism effect of PTGS2 in vitro and in vivo. The results indicated that PTGS2 was the downstream molecule of amentoflavone, which was highly expressed in IL-1β-stimulated chondrocytes and KOA rats, and amentoflavone decreased PTGS2 expression. We also confirmed the potential role of amentoflavone on KOA, which was also characterized by the repair of cartilage injury, reduction of inflammatory infiltration, and improvement of functional disability. Consistent with in vivo results, in vitro experiments gave the same conclusions. Amentoflavone reduced PTGS2 expression in IL-1β-stimulated chondrocytes and inhibited inflammation of chondrocytes via PTGS2. Collectively, the results confirmed that this drug was the potential targeted drug for KOA, whose repair effect on cartilage injury was partly related to PTGS2.

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Funding

This work was supported by grants from Focus on Research and Development Plan in Shandong province (2016GSF201112), the Shandong Medicine and Health Science and Technology Development Plan Project (2016WS0696), and the Major research program of Science and Technology Bureau in Yantai City (2016WS033).

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  1. Yiheng Cheng and Xiaofeng Liu equally contributed to this work.

Authors and Affiliations

  1. Department of Orthopaedics, Yantaishan Hospital, Yantai, 264000, Shandong, China

    Yiheng Cheng, Wenqing Qu & Wenliang Li

  2. Department of Traumatic Orthopaedics, Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shandong, China

    Xiaofeng Liu, Xin Wang & Hao Su

  3. Department of Hand and Foot Surgery, Yantai Yuhuangding Hospital of Qingdao University, 20 Yuhuangding East Road, Yantai, 264000, Shandong, China

    Wenqiang Xu

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  1. Yiheng Cheng
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Contributions

All authors contributed to the study conception and design. Material preparation was performed by Yiheng Cheng and Xiaofeng Liu. Data collection and analysis were performed by Wenqing Qu, Xin Wang, Hao Su, and Wenliang Li. The first draft of the manuscript was written by Wenqiang Xu, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Wenqiang Xu.

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Cheng, Y., Liu, X., Qu, W. et al. Amentoflavone alleviated cartilage injury and inflammatory response of knee osteoarthritis through PTGS2. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03222-4

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