Green tea polyphenol treatment is chondroprotective, anti-inflammatory and palliative in a mouse post-traumatic osteoarthritis model

Daniel J. Leong, Marwa Choudhury, Regina Hanstein, David M. Hirsh, Sun Jin Kim, Robert J. Majeska, Mitchell B. Schaffler, John A. Hardin, David C. Spray, Mary B. Goldring, Neil J. Cobelli, Hui (Herb) Sun

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)508
Number of pages1
JournalArthritis Research and Therapy
Volume16
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Polyphenols
Tea
Osteoarthritis
Anti-Inflammatory Agents
Articular Cartilage
Matrix Metalloproteinase 13
Tibial Meniscus
Aggrecans
Pain
Therapeutics
Collagen Type II
Spinal Ganglia
Staining and Labeling
Interleukin-1
Cartilage
Real-Time Polymerase Chain Reaction
Tumor Necrosis Factor-alpha
Cytokines
Thrombospondins
Disintegrins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Green tea polyphenol treatment is chondroprotective, anti-inflammatory and palliative in a mouse post-traumatic osteoarthritis model. / Leong, Daniel J.; Choudhury, Marwa; Hanstein, Regina; Hirsh, David M.; Kim, Sun Jin; Majeska, Robert J.; Schaffler, Mitchell B.; Hardin, John A.; Spray, David C.; Goldring, Mary B.; Cobelli, Neil J.; Sun, Hui (Herb).

In: Arthritis Research and Therapy, Vol. 16, No. 6, 2014, p. 508.

Research output: Contribution to journalArticle

Leong, Daniel J. ; Choudhury, Marwa ; Hanstein, Regina ; Hirsh, David M. ; Kim, Sun Jin ; Majeska, Robert J. ; Schaffler, Mitchell B. ; Hardin, John A. ; Spray, David C. ; Goldring, Mary B. ; Cobelli, Neil J. ; Sun, Hui (Herb). / Green tea polyphenol treatment is chondroprotective, anti-inflammatory and palliative in a mouse post-traumatic osteoarthritis model. In: Arthritis Research and Therapy. 2014 ; Vol. 16, No. 6. pp. 508.
@article{9648395df6b34653930b2b6a6c44cec7,
title = "Green tea polyphenol treatment is chondroprotective, anti-inflammatory and palliative in a mouse post-traumatic osteoarthritis model",
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.",
author = "Leong, {Daniel J.} and Marwa Choudhury and Regina Hanstein and Hirsh, {David M.} and Kim, {Sun Jin} and Majeska, {Robert J.} and Schaffler, {Mitchell B.} and Hardin, {John A.} and Spray, {David C.} and Goldring, {Mary B.} and Cobelli, {Neil J.} and Sun, {Hui (Herb)}",
year = "2014",
doi = "10.1186/s13075-014-0508-y",
language = "English (US)",
volume = "16",
pages = "508",
journal = "Arthritis Research and Therapy",
issn = "1478-6354",
publisher = "BioMed Central",
number = "6",

}

TY - JOUR

T1 - Green tea polyphenol treatment is chondroprotective, anti-inflammatory and palliative in a mouse post-traumatic osteoarthritis model

AU - Leong, Daniel J.

AU - Choudhury, Marwa

AU - Hanstein, Regina

AU - Hirsh, David M.

AU - Kim, Sun Jin

AU - Majeska, Robert J.

AU - Schaffler, Mitchell B.

AU - Hardin, John A.

AU - Spray, David C.

AU - Goldring, Mary B.

AU - Cobelli, Neil J.

AU - Sun, Hui (Herb)

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84965191641&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84965191641&partnerID=8YFLogxK

U2 - 10.1186/s13075-014-0508-y

DO - 10.1186/s13075-014-0508-y

M3 - Article

C2 - 25516005

AN - SCOPUS:84924336138

VL - 16

SP - 508

JO - Arthritis Research and Therapy

JF - Arthritis Research and Therapy

SN - 1478-6354

IS - 6

ER -