Wogonoside inhibits IL-1β induced catabolism and hypertrophy in mouse chondrocyte and ameliorates murine osteoarthritis
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Qian Tang1,2, Gang Zheng1,2, Zhenhua Feng1,2, Minji Tong1,2, Jianxiang Xu1,2, Zhiyan Hu4, Ping Shang3, Yu Chen1, Chenggui Wang1,2, Yiting Lou1,2, Deheng Chen1,2, Di Zhang1,2, Majid Nisar1,2, Xiaolei Zhang1,2, Huazi Xu1,2 and Haixiao Liu1,2
1Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 325027 Wenzhou, China
2Zhejiang Provincial Key Laboratory of Orthopaedics, 325027 Wenzhou, China
3Department of Rehabilitation, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 325027 Wenzhou, China
4Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 325027 Wenzhou, China
Haixiao Liu, email: email@example.com
Huazi Xu, email: firstname.lastname@example.org
Xiaolei Zhang, email: email@example.com
Keywords: wogonoside, osteoarthritis, NF-κB, HIF-2α, hypertrophy
Received: January 25, 2017 Accepted: April 27, 2017 Published: June 06, 2017
The inflammatory environment is correlated with extracellular matrix (ECM) degradation and chondrocyte hypertrophy in the development of osteoarthritis (OA). Previous studies have reported the anti-inflammatory effects of wogonoside in several diseases. In the present study, we investigated the protective effects of wogonoside in relation to the development of OA and delineated the potential mechanism. In vitro, wogonoside decreased the production of pro-inflammatory cytokines like Nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). It also inhibited the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) both at gene and protein levels. Wogonoside also inhibited hypertrophy and the generation of vascular endothelial growth factor (VEGF) in interleukin-1β (IL-1β)-induced chondrocytes. Moreover, wogonoside promoted the expression of anabolic factors Sox-9, type two collagen and aggrecan while inhibiting the expression of catabolic factors such as matrix metalloproteinases (MMPs) and thrombospondin motifs 5 (ADAMTS-5) in mouse chondrocytes. Mechanistically, we found that wogonoside inhibited nuclear factor kappa B/ hypoxia-inducible factor two alpha (NF-κB/HIF-2α) activation via the phosphatidylinositol 3 kinase (PI3K) /AKT pathway. The protective effects of wogonoside were also observed in vivo and the pharmacokinetic results of wogonoside indicated that good systemic exposure was achievable after oral administration of wogonoside. In conclusion, our stduy demonstrates that wogonoside attenuates IL-1β-induced ECM degradation and hypertrophy in mouse chondrocytes via suppressing the activation of NF-κB/HIF-2α by the PI3K/AKT pathway. Moreover, wogonoside ameliorates OA progression in vivo, indicating that wogonoside may serve as a promising therapeutic agent for the treatment of OA.
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