Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification

被引:170
作者
Morita, Kozo
Miyamoto, Takeshi [1 ]
Fujita, Nobuyuki
Kubota, Yoshiaki
Ito, Keisuke
Takubo, Keiyo
Miyamoto, Kana
Ninomiya, Ken
Suzuki, Torn
Iwasaki, Ryotaro
Yagi, Mitsuru
Takaishi, Hironari
Toyama, Yoshiaki
Suda, Toshio
机构
[1] Keio Univ, Sch Med, Dept Cell Differentiat, Sakaguchi Lab Dev Biol,Shinjuku Ku, Tokyo 1608582, Japan
[2] Keio Univ, Sch Med, Dept Orthoped Surg, Shinjuku Ku, Tokyo 1608582, Japan
[3] Keio Univ, Sch Med, Dept Musculoskeletal Resconstruct & Regenerat, Shinjuku Ku, Tokyo 1608582, Japan
[4] Keio Univ, Sch Med, Dept Dent & Oral Surg, Shinjuku Ku, Tokyo 1608582, Japan
关键词
D O I
10.1084/jem.20062525
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 1 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.
引用
收藏
页码:1613 / 1623
页数:11
相关论文
共 31 条
[11]   The role of reactive oxygen species in homeostasis and degradation of cartilage [J].
Henrotin, YE ;
Bruckner, P ;
Pujol, JPL .
OSTEOARTHRITIS AND CARTILAGE, 2003, 11 (10) :747-755
[12]   Smad6/Smurf1 overexpression in cartilage delays chondrocyte hypertrophy and causes dwarfism with osteopenia [J].
Horiki, M ;
Imamura, T ;
Okamoto, M ;
Hayashi, M ;
Murai, J ;
Myoui, A ;
Ochi, T ;
Miyazono, K ;
Yoshikawa, H ;
Tsumaki, N .
JOURNAL OF CELL BIOLOGY, 2004, 165 (03) :433-445
[13]   Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells [J].
Ito, K ;
Hirao, A ;
Arai, F ;
Matsuoka, S ;
Takubo, K ;
Hamaguchi, I ;
Nomiyama, K ;
Hosokawa, K ;
Sakurada, K ;
Nakagata, N ;
Ikeda, Y ;
Mak, TW ;
Suda, T .
NATURE, 2004, 431 (7011) :997-1002
[14]   Neuroprotective effect of N-acetyl cysteine on hypoxia-induced oxidative stress in primary hippocampal culture [J].
Jayalakshmi, K ;
Sairam, M ;
Singh, SB ;
Sharma, SK ;
Ilavazhagan, G ;
Banerjee, PK .
BRAIN RESEARCH, 2005, 1046 (1-2) :97-104
[15]   Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts [J].
Komori, T ;
Yagi, H ;
Nomura, S ;
Yamaguchi, A ;
Sasaki, K ;
Deguchi, K ;
Shimizu, Y ;
Bronson, RT ;
Gao, YH ;
Inada, M ;
Sato, M ;
Okamoto, R ;
Kitamura, Y ;
Yoshiki, S ;
Kishimoto, T .
CELL, 1997, 89 (05) :755-764
[16]   Developmental regulation of the growth plate [J].
Kronenberg, HM .
NATURE, 2003, 423 (6937) :332-336
[17]  
Manton Kenneth G., 2004, Current Alzheimer Research, V1, P277, DOI 10.2174/1567205043332036
[18]  
MATSUMOTO H, 1991, J BONE MINER RES, V6, P569
[19]   The anti-aging sweepstakes: Catalase runs for the ROSes [J].
Miller, RA .
SCIENCE, 2005, 308 (5730) :1875-1876
[20]   Role of hydrogen peroxide in the aetiology of Alzheimer's disease - Implications for treatment [J].
Milton, NGN .
DRUGS & AGING, 2004, 21 (02) :81-100