Rutaecarpine ameliorates osteoarthritis by inhibiting PI3K/AKT/NF‑κB and MAPK signalling transduction through integrin αVβ3

Wan,Junlai; Li,Mengwei; Yuan,Xi; Yu,Xiaojun; Chen,Anmin; Shao,Ming; Kang,Hao; Cheng,Peng

doi:10.3892/ijmm.2023.5300

Rutaecarpine ameliorates osteoarthritis by inhibiting PI3K/AKT/NF‑κB and MAPK signalling transduction through integrin αVβ3

Authors:
- Junlai Wan
- Mengwei Li
- Xi Yuan
- Xiaojun Yu
- Anmin Chen
- Ming Shao
- Hao Kang
- Peng Cheng
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Affiliations: Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Orthopaedics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510530, P.R. China, Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: August 29, 2023 https://doi.org/10.3892/ijmm.2023.5300
Article Number: 97
Copyright: © Wan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteoarthritis (OA) is a chronic progressive articular illness which commonly affects older‑aged adults, presenting with cartilage inflammation and degradation. Rutaecarpine (RUT) has been shown to exert promising anti‑inﬂammatory effects; however, the efficacy of RUT in the treatment of OA is debatable. The present study investigated the potential of RUT in alleviating OA in a mouse model. Treatment with RUT inhibited the inﬂammatory response and extracellular matrix degradation by suppressing process regulators in interleukin (IL)‑1β‑stimulated chondrocytes. Moreover, treatment with RUT in vitro upregulated the gene expression of anabolic agents, such as collagen type II, aggrecan and SRY‑box transcription factor 9, indicating that RUT contributed to cartilage repair. Additionally, flow cytometric assays, and the measurement of β‑galactosidase levels, autophagic flux and related protein expression revealed that RUT effectively attenuated IL‑1β‑induced chondrocyte apoptosis, senescence and autophagy impairment. In addition, bioinformatics analysis and in vitro experiments demonstrated that RUT protected cartilage by mediating the phosphoinositide‑3‑kinase (PI3K)/Akt/nuclear factor‑κB (NF‑κB) and mitogen‑activated protein kinase (MAPK) pathways. The ameliorative effects of RUT on IL‑1β‑stimulated chondrocytes were abrogated when siRNA was used to knock down integrin αVβ3. Furthermore, the results of immunohistochemical analysis and microcomputed tomography confirmed the in vivo therapeutic effects of RUT in mice with OA. On the whole, the present study demonstrates that RUT attenuates the inflammatory response and cartilage degradation in mice with OA by suppressing the activation of the PI3K/AKT/NF‑κB and MAPK pathways. Integrin αVβ3 may play a pivotal role in these effects.

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