Green tea polyphenol treatment is chondroprotective, anti-inflammatory and palliative in a mouse post-traumatic osteoarthritis model
Authors: Hui B Sun
Marwa Choudhury
David C Spray
Daniel J Leong
David M Hirsh
Mitchell B Schaffler
Mary B Goldring
John A Hardin
Robert J Majeska
Regina Hanstein
Sun Jin Kim
Neil J Cobelli
Journal: Arthritis Research & Therapy (2014)
Discipline: CLINICAL MEDICINE
Keywords: EGCG; osteoarthritis; chondroprotective effects; mouse model; cartilage erosion

Abstract:  Introduction: Epigallocatechin 3-gallate (EGCG), a polyphenol present in green tea, was shown to exert chondroprotective effects in vitro. In this study, we used a post-traumatic osteoarthritis (OA) mouse model to test whether EGCG could slow the progression of OA and relieve OA-associated pain. Methods: C57BL/6 mice were subjected to surgical destabilization of the medial meniscus (DMM) or sham surgery. EGCG (25 mg/kg) or vehicle control was administered daily for four or eight weeks by intraperitoneal injection starting on the day of surgery. OA severity was evaluated by Safranin O staining and Osteoarthritis Research Society International (OARSI) score, and by immunohistochemical analysis to detect cleaved aggrecan and type II collagen, and expression of proteolytic enzymes matrix metalloproteinase (MMP)-13 and A Disintegrin And Metalloproteinase with Thrombospondin Motifs (ADAMTS5). Real-time polymerase chain reaction (PCR) was performed to characterize the expression of genes critical for articular cartilage homeostasis. During the course of the experiments, tactile sensitivity testing (von Frey test) and open field assays were used to evaluate pain behaviors associated with OA, and expression of pain expression markers and inflammatory cytokines in the dorsal root ganglion (DRG) were determined by real-time PCR. Results: Four and eight weeks after DMM surgery, the cartilage in EGCG-treated mice exhibited less Safranin O loss and cartilage erosion, and lower OARSI scores compared to vehicle-treated controls, which was associated with reduced staining for aggrecan and type II collagen cleavage epitopes, and reduced staining for MMP-13 and ADAMTS5 in the articular cartilage. Articular cartilage in the EGCG-treated mice also exhibited reduced levels of MMP-1, -3, -8, -13, ADAMTS5, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α mRNA and elevated gene expression of the MMP regulator Cbp/p300 Interacting Transactivator 2 (CITED2). Compared to vehicle controls, mice treated with EGCG exhibited reduced OA-associated pain, as indicated by higher locomotor behavior (i.e. distance traveled). Moreover, expression of chemokine receptor (CCR2), and pro-inflammatory cytokines IL-1β and TNF-α in the DRG were significantly reduced to levels similar to sham-operated animals. Conclusions: This study provides the first evidence in an OA animal model that EGCG significantly slows OA disease progression and exerts a palliative effect. 

Retracted: No

PubPeer comments:
 see ORI research misconduct finding item #8 https: ori.hhs.gov content case-summary-leong-daniel Respondent reused and relabeled photomicrographs from the following published papers to falsely represent unrelated experimental results in NIH grant applications: Green tea polyphenol treatment is chondroprotective, anti-inflammatory and palliative in a mouse post-traumatic osteoarthritis model. Arthritis Res Ther. 2014 Dec 17;16(6):508; doi: 10.1186 sl3075-014-0508-y (hereafter referred to as u201cArthritis Res Ther. 2014u201d). note ORI doi is wrong. should be: 10.1186 s13075-014-0508-y [have letter l rather than number 1 ] Erratum in: Arthritis Res Ther. 2019, Jan 3;21(1):1; doi: 10.1186 s13075-018-1791-9. Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model. Arthritis Res Ther. 2016 Jun 3; 18(1):128; doi: 10.1186 s13075-016-1025-y (hereafter referred to as u201cArthritis Res Ther. 2016u201d). ,