Intra-Articular Injection of (-)-Epigallocatechin 3-Gallate (EGCG) Ameliorates Cartilage Degeneration in Guinea Pigs with Spontaneous Osteoarthritis.

Hsuan-Ti Huang,Jhong-You Li,Chi-Fen Chang,Shih-Hao Huang,Hsin-Yi Shen,Shu-Chun Chuang,Yi-Shan Lin,Lin Kang,Tsung-Han Yu,Chung-Hwan Chen,Tsung-Lin Cheng,Cheng-Jung Ho,Chung-Da Yang,Sung-Yen Lin

doi:10.3390/antiox10020178

Abstract

Osteoarthritis (OA) is the most prevalent joint disease that causes an enormous burden of disease worldwide. (−)-Epigallocatechin 3-gallate (EGCG) has been reported to reduce post-traumatic OA progression through its anti-inflammatory property. Aging is the most crucial risk factor of OA, and the majority of OA incidences are related to age and not trauma. In this study, we assess whether EGCG can ameliorate cartilage degradation in primary OA. In an in-vitro study, real-time PCR was performed to assess the expression of genes associated with human articular chondrocyte homeostasis. A spontaneously occurring OA model in guinea pigs was used to investigate the effect of EGCG in vivo. OA severity was evaluated using Safranin O staining and Osteoarthritis Research Society International (OARSI) scores, as well as by immunohistochemical (IHC) analysis to determine the protein level of type II collagen (Col II), matrix metalloproteinase 13 (MMP-13), and p16 ink4a in articular cartilage. In the in-vitro study, EGCG increased the gene expression of aggrecan and Col II and decreased the expression of interleukin-1, cyclooxygenase 2, MMP-13, alkaline phosphatase, Col X, and p16 Ink4a; EGCG treatment also attenuated the degraded cartilage with a lower OARSI score. Meanwhile, IHC results showed that EGCG exerted an anti-OA effect by reducing ECM degradation, cartilage inflammation, and cell senescence with a less-immunostained Col II, MMP-13, and p16 Ink4a. In conclusion, these findings suggest that EGCG may be a potential disease-modifying OA drug for the treatment of primary OA.

Highlights

Osteoarthritis (OA) is an age-related disease that is considered to be the leading cause of functional disability in the older population [1]
The results revealed that the immunostained MMP-13 protein increased with aging and the treatment of Epigallocatechin 3-gallate (EGCG) decreased the staining of MMP-13 compared with the control group at 9 months of age (Figure 7A)
In this study, we further found that the levels of p16 Ink4a gene expression and SAβGal activity were markedly decreased in IL-1β-stimulated HAC after EGCG treatment, indicating EGCG may attenuate chondrocyte cell senescence after IL-1β stimulation

Summary

Introduction

Osteoarthritis (OA) is an age-related disease that is considered to be the leading cause of functional disability in the older population [1]. The chondroprotective effect of EGCG has been widely investigated using human articular chondrocytes [22,23,24], animal articular chondrocytes [25,26], bovine cartilage explants [27], and surgically induced OA animal models [28,29,30]. These studies have demonstrated that EGCG could mitigate OA progression by inhibiting the expression of proinflammatory genes (i.e., cyclooxygenase 2 (COX-2), matrix metalloproteinase-1(MMP-1), MMP-3, MMP-13, inducible nitric oxide synthase, tumor necrosis factor-α (TNF-α), transforming growth factor-β2, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, aggrecanase-1, -2) [22,23,26,28,31,32,33], reducing the production of nitric oxide [22,34] and prostaglandin E2 [32,35], as well as increasing chondrogenic regeneration genes (i.e., aggrecan, collagen type II (Col II), and SOX9) [25,28]

Methods

Results

Discussion

Conclusion