Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model

Yosuke Kaneko, Nobuharu Tanigawa, Yuiko Sato, Tami Kobayashi, Satoshi Nakamura, Eri Ito, Tomoya Soma, Kana Miyamoto, Shu Kobayashi, Kengo Harato, Morio Matsumoto, Masaya Nakamura, Yasuo Niki, Takeshi Miyamoto

Research output: Contribution to journalArticle

Abstract

The number of osteoarthritis patients is increasing with the rise in the number of elderly people in developed countries. Osteoarthritis, which causes joint pain and deformity leading to loss of activities of daily living, is often treated surgically. Here we show that mechanical stress promotes accumulation of reactive oxygen species (ROS) in chondrocytes in vivo, resulting in chondrocyte apoptosis and leading to osteoarthritis development in a rat model. We demonstrate that mechanical stress induces ROS accumulation and inflammatory cytokine expression in cultured chondrocytes in vitro and that both are inhibited by treatment with the anti-oxidant N-acetyl cysteine (NAC). In vivo, osteoarthritis development in a rat osteoarthritis model was also significantly inhibited by oral administration of NAC. MMP13 expression and down-regulation of type II collagen in chondrocytes, both of which indicate osteoarthritis, as well as chondrocyte apoptosis in osteoarthritis rats were inhibited by NAC. Interestingly, osteoarthritis development in sham-operated control sides, likely due to disruption of normal weight-bearing activity on the control side, was also significantly inhibited by NAC. We conclude that osteoarthritis development in rats is significantly antagonized by oral NAC administration. Currently, no oral medication is available to prevent osteoarthritis development. Our work suggests that NAC may represent such a reagent and serve as osteoarthritis treatment.

Original languageEnglish
Number of pages1
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 10

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Osteoarthritis
Cysteine
Oral Administration
Chondrocytes
Mechanical Stress
Reactive Oxygen Species
Apoptosis
Collagen Type II
Weight-Bearing
Arthralgia
Activities of Daily Living
Developed Countries
Oxidants
Down-Regulation
Cytokines
Therapeutics

ASJC Scopus subject areas

  • General

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Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model. / Kaneko, Yosuke; Tanigawa, Nobuharu; Sato, Yuiko; Kobayashi, Tami; Nakamura, Satoshi; Ito, Eri; Soma, Tomoya; Miyamoto, Kana; Kobayashi, Shu; Harato, Kengo; Matsumoto, Morio; Nakamura, Masaya; Niki, Yasuo; Miyamoto, Takeshi.

In: Scientific reports, Vol. 9, No. 1, 10.12.2019.

Research output: Contribution to journalArticle

Kaneko, Yosuke ; Tanigawa, Nobuharu ; Sato, Yuiko ; Kobayashi, Tami ; Nakamura, Satoshi ; Ito, Eri ; Soma, Tomoya ; Miyamoto, Kana ; Kobayashi, Shu ; Harato, Kengo ; Matsumoto, Morio ; Nakamura, Masaya ; Niki, Yasuo ; Miyamoto, Takeshi. / Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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