Anti-inflammatory and anti-osteoarthritis effects of tectorigenin.

Cheng-Long Wang,Chuan-Dong Wang,Xiao-Ling Zhang,Fei Xiao,Yi-Min Cui,De Li,Guo-Li Hu,Chao Shen,Xiao-Dong Chen,Yuan Gao,Hui Wang,Jun-Feng Zhu,Bin Zuo

doi:10.1242/bio.024562

Abstract

ABSTRACTOsteoarthritis (OA) is a common and dynamic disease of the joints, including the articular cartilage, underlying bones and synovium. In particular, OA is considered as the degeneration of the cartilage. Tectorigenin (Tec) is known to affect many biological processes; however, its effects on articular chondrocytes remain unclear. This study aimed to assess the effects of Tec on articular cartilage. In vitro, Tec inhibited the expression levels of type X collagen, cyclooxigenase-2, matrix metalloproteinase (MMP)-3 and MMP-13, but enhanced the expression of Runx1, type II collagen and aggrecan in the presence of IL-1β. Meanwhile, Tec inhibited apoptosis through the Bax/Bcl-2/caspase-3 pathway, upregulating p-Bad, downregulating the Bax/Bcl-2 ratio, and activating caspase-3 compared with IL-1β treatment only. Moreover, this process was partially regulated by NF-κB P65. In vivo, the chondroprotective effects of Tec were assessed by establishing a model of surgically induced OA. Tec-treated joints exhibited fewer osteoarthritic changes than saline-treated joints. Meanwhile, 1.5 μg/kg Tec treatment produced a greater protective effect than 0.75 μg/kg Tec. The Osteoarthritis Research Society International (OARSI) scoring system, employed to assess histopathological grading of the models, as well immunohistochemistry for Aggrecan Neoepitope and MMP-3, further confirmed the results. In conclusion, this study showed that Tec plays a chondroprotective role in the OA process by preventing articular cartilage degeneration and chondrocyte apoptosis via the NF-κB P65 pathway.

Highlights

Osteoarthritis (OA) is a common joint disease, regarded as a local inflammatory response caused by joint instability and accompanied by the progressive degeneration of articular cartilage (Feldmann, 2001), in sites where stress exceeds the value that can be sustained by the joint
The destructive effect is contributed by cyclooxigenase-2 (Cox-2), which produces prostaglandin E2 (PGE2), resulting in inflammation and pain in OA (Pelletier et al, 2001; Lianxu et al, 2006)
Cox-2 harms the superficial layers of articular cartilage, and the NF-κB pathway plays an important role during the process

Summary

Introduction

Osteoarthritis (OA) is a common joint disease, regarded as a local inflammatory response caused by joint instability and accompanied by the progressive degeneration of articular cartilage (Feldmann, 2001), in sites where stress exceeds the value that can be sustained by the joint. Given the aging population in the developed world, the prevalence of OA is. During the OA process, a number of inflammatory mediators have been reported (Chabane et al, 2008). Interleukin (IL) 1β is considered a main inflammatory mediator resulting in the occurrence of OA by damaging articular cartilage via NF-κB pathway activation (Chabane et al, 2008); (Goldring and Berenbaum, 1999; Newton et al, 1997). Cox-2 harms the superficial layers of articular cartilage, and the NF-κB pathway plays an important role during the process

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