Sulfasalazine attenuates ACL transection and medial menisectomy-induced cartilage destruction by inhibition of cystine/glutamate antiporter

Wei Yuan Tsai, Ru Yin Tsai, Chih Chung Liu, Jia-Lin Wu, Chih Shung Wong

研究成果: 雜誌貢獻文章

3 引文 (Scopus)

摘要

We had previously demonstrated that excitatory amino acid glutamate plays a role in the progression and severity of knee osteoarthritis (OA), and early hyaluronic acid injection attenuates the OA progression by attenuation of knee joint glutamate level, which was also related to the cystine/glutamate antiporter system X (system XC-) expression. System XC- uptakes cystine into chondrocytes for glutathione (GSH) synthesis, but the role of system XC- in OA is rarely addressed. Sulfasalazine (SSZ) is a system XC- inhibitor; SSZ was applied intra-articularly to study the function of system XC- in the development of OA in rats subjected to anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx). Moerover, the system XC- activator N-acetylcysteine (NAC) was also applied to verify the role of system XC-. The intra-articular injection of SSZ significantly attenuated knee swelling and cartilage destruction in the knees of ACLT + MMx rats and this effect was blocked by NAC. The results showed that inhibition of system XC- function can attenuate ACLT + MMx-induced cartilage destruction. In the present study, system XC- inhibitor SSZ was shown to reduce glutamate content in synovial fluid and GSH in chondrocytes. It was also showed SSZ could attenuate ACLT + MMx-induced cartilage destruction, and treatment of NAC reversed the protective effect of SSZ.
原文英語
頁(從 - 到)650-7
頁數8
期刊Journal of Orthopaedic Research
34
發行號4
DOIs
出版狀態已發佈 - 四月 2016

指紋

Antiporters
Sulfasalazine
Cystine
Cartilage
Glutamic Acid
Acetylcysteine
Osteoarthritis
Chondrocytes
Knee
Intra-Articular Injections
Excitatory Amino Acids
Knee Osteoarthritis
Anterior Cruciate Ligament
Synovial Fluid
Hyaluronic Acid
Knee Joint
Glutathione
Injections

引用此文

@article{2629b5bdca1d4839b8a4b6f30ae0d6ee,
title = "Sulfasalazine attenuates ACL transection and medial menisectomy-induced cartilage destruction by inhibition of cystine/glutamate antiporter",
abstract = "We had previously demonstrated that excitatory amino acid glutamate plays a role in the progression and severity of knee osteoarthritis (OA), and early hyaluronic acid injection attenuates the OA progression by attenuation of knee joint glutamate level, which was also related to the cystine/glutamate antiporter system X (system XC-) expression. System XC- uptakes cystine into chondrocytes for glutathione (GSH) synthesis, but the role of system XC- in OA is rarely addressed. Sulfasalazine (SSZ) is a system XC- inhibitor; SSZ was applied intra-articularly to study the function of system XC- in the development of OA in rats subjected to anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx). Moerover, the system XC- activator N-acetylcysteine (NAC) was also applied to verify the role of system XC-. The intra-articular injection of SSZ significantly attenuated knee swelling and cartilage destruction in the knees of ACLT + MMx rats and this effect was blocked by NAC. The results showed that inhibition of system XC- function can attenuate ACLT + MMx-induced cartilage destruction. In the present study, system XC- inhibitor SSZ was shown to reduce glutamate content in synovial fluid and GSH in chondrocytes. It was also showed SSZ could attenuate ACLT + MMx-induced cartilage destruction, and treatment of NAC reversed the protective effect of SSZ.",
keywords = "Animals, Anterior Cruciate Ligament, Antiporters, Antirheumatic Agents, Cells, Cultured, Chondrocytes, Drug Evaluation, Preclinical, Knee Injuries, Male, Menisci, Tibial, Osteoarthritis, Knee, Rats, Wistar, Sulfasalazine, Journal Article, Research Support, Non-U.S. Gov't",
author = "Tsai, {Wei Yuan} and Tsai, {Ru Yin} and Liu, {Chih Chung} and Jia-Lin Wu and Wong, {Chih Shung}",
note = "{\circledC} 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.",
year = "2016",
month = "4",
doi = "10.1002/jor.23069",
language = "English",
volume = "34",
pages = "650--7",
journal = "Journal of Orthopaedic Research",
issn = "0736-0266",
publisher = "John Wiley and Sons Inc.",
number = "4",

}

TY - JOUR

T1 - Sulfasalazine attenuates ACL transection and medial menisectomy-induced cartilage destruction by inhibition of cystine/glutamate antiporter

AU - Tsai, Wei Yuan

AU - Tsai, Ru Yin

AU - Liu, Chih Chung

AU - Wu, Jia-Lin

AU - Wong, Chih Shung

N1 - © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

PY - 2016/4

Y1 - 2016/4

N2 - We had previously demonstrated that excitatory amino acid glutamate plays a role in the progression and severity of knee osteoarthritis (OA), and early hyaluronic acid injection attenuates the OA progression by attenuation of knee joint glutamate level, which was also related to the cystine/glutamate antiporter system X (system XC-) expression. System XC- uptakes cystine into chondrocytes for glutathione (GSH) synthesis, but the role of system XC- in OA is rarely addressed. Sulfasalazine (SSZ) is a system XC- inhibitor; SSZ was applied intra-articularly to study the function of system XC- in the development of OA in rats subjected to anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx). Moerover, the system XC- activator N-acetylcysteine (NAC) was also applied to verify the role of system XC-. The intra-articular injection of SSZ significantly attenuated knee swelling and cartilage destruction in the knees of ACLT + MMx rats and this effect was blocked by NAC. The results showed that inhibition of system XC- function can attenuate ACLT + MMx-induced cartilage destruction. In the present study, system XC- inhibitor SSZ was shown to reduce glutamate content in synovial fluid and GSH in chondrocytes. It was also showed SSZ could attenuate ACLT + MMx-induced cartilage destruction, and treatment of NAC reversed the protective effect of SSZ.

AB - We had previously demonstrated that excitatory amino acid glutamate plays a role in the progression and severity of knee osteoarthritis (OA), and early hyaluronic acid injection attenuates the OA progression by attenuation of knee joint glutamate level, which was also related to the cystine/glutamate antiporter system X (system XC-) expression. System XC- uptakes cystine into chondrocytes for glutathione (GSH) synthesis, but the role of system XC- in OA is rarely addressed. Sulfasalazine (SSZ) is a system XC- inhibitor; SSZ was applied intra-articularly to study the function of system XC- in the development of OA in rats subjected to anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx). Moerover, the system XC- activator N-acetylcysteine (NAC) was also applied to verify the role of system XC-. The intra-articular injection of SSZ significantly attenuated knee swelling and cartilage destruction in the knees of ACLT + MMx rats and this effect was blocked by NAC. The results showed that inhibition of system XC- function can attenuate ACLT + MMx-induced cartilage destruction. In the present study, system XC- inhibitor SSZ was shown to reduce glutamate content in synovial fluid and GSH in chondrocytes. It was also showed SSZ could attenuate ACLT + MMx-induced cartilage destruction, and treatment of NAC reversed the protective effect of SSZ.

KW - Animals

KW - Anterior Cruciate Ligament

KW - Antiporters

KW - Antirheumatic Agents

KW - Cells, Cultured

KW - Chondrocytes

KW - Drug Evaluation, Preclinical

KW - Knee Injuries

KW - Male

KW - Menisci, Tibial

KW - Osteoarthritis, Knee

KW - Rats, Wistar

KW - Sulfasalazine

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/jor.23069

DO - 10.1002/jor.23069

M3 - Article

C2 - 26466556

VL - 34

SP - 650

EP - 657

JO - Journal of Orthopaedic Research

JF - Journal of Orthopaedic Research

SN - 0736-0266

IS - 4

ER -