Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification

Kozo Morita, Takeshi Miyamoto, Nobuyuki Fujita, Yoshiaki Kubota, Keisuke Ito, Keiyo Takubo, Kana Miyamoto, Ken Ninomiya, Toru Suzuki, Ryotaro Iwasaki, Mitsuru Yagi, Hironari Takaishi, Yoshiaki Toyama, Toshio Suda

研究成果: Article査読

139 被引用数 (Scopus)

抄録

Chondrocyte hypertrophy during endochondral ossification is a well-controlled process in which proliferating chondrocytes stop proliferating and differentiate into hypertrophic chondrocytes, which then undergo apoptosis. Chondrocyte hypertrophy induces angiogenesis and mineralization. This step is crucial for the longitudinal growth and development of long bones, but what triggers the process is unknown. Reactive oxygen species (ROS) have been implicated in cellular damage; however, the physiological role of ROS in chondrogenesis is not well characterized. We demonstrate that increasing ROS levels induce chondrocyte hypertrophy. Elevated ROS levels are detected in hypertrophic chondrocytes. In vivo and in vitro treatment with N-acetyl cysteine, which enhances endogenous antioxidant levels and protects cells from oxidative stress, inhibits chondrocyte hypertrophy. In ataxia telangiectasia mutated ( Atm)-deficient ( Atm-/-) mice, ROS levels were elevated in chondrocytes of growth plates, accompanied by a proliferation defect and stimulation of chondrocyte hypertrophy. Decreased proliferation and excessive hypertrophy in Atm-/- mice were also rescued by antioxidant treatment. These findings indicate that ROS levels regulate inhibition of proliferation and modulate initiation of the hypertrophic changes in chondrocytes. JEM

本文言語English
ページ(範囲)1613-1623
ページ数11
ジャーナルJournal of Experimental Medicine
204
7
DOI
出版ステータスPublished - 2007 7月 9

ASJC Scopus subject areas

  • 医学(全般)

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