| Homocysteine Enhances Bone Resorption by Stimulation of Osteoclast Formation and Activity via Increased Intracellular ROS Generation |
| 호모시스테인에 의한 세포내 산화 스트레스 증가가 파골세포 형성 및 활동성에 미치는 영향 |
| 이영선1,김양순1,고정민2,김기수2 |
| 아산생명과학 연구소1, 울산대학교 의과대학 서울아산병원 내과학교실2 |
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| Abstract |
Background
Hyperhomocysteinemia is a modifiable risk factor for osteoporosis and its related bone fractures. It has been reported that bone resorption and turnover rate were increased in hyperhomocysteinemia. Using mouse bone marrow cells, we examined the direct effects of homocysteine (Hcy) on osteoclast formation and activity.
Methods
Osteoclast formation was determined by tartrate-resistant acid phosphatase (TRAP) staining and TRAP activity. Intracellular reactive oxygen species (ROS) generation was measured using a fluorescent probe, dichlorodihydrofluorescein diacetate. Intracellular signaling cascades of p38 MAPK, ERK, JNK and NFκB were measured by western blotting. Integrin β3 mRNA levels were measured by reverse transcription-polymerase chain reaction. Actin ring formation and bone resorption assays were also performed.
Results
Physiologic concentrations of Hcy upregulated TRAP-positive multinucleated cells and TRAP activity, stimulated actin ring formation, and increased the number of nuclei per cell and the level of expression of integrin β3 mRNA. In addition, Hcy increased bone resorption and stimulated p38 MAPK activity and intracellular ROS generation. All of these Hcy-induced changes were blocked by pretreatment with the antioxidant, N-acetyl cysteine.
Conclusions
Hcy directly activates osteoclast formation and activity via increased generation of intracellular ROS. These findings suggest that, in individuals with mild to moderate hyperhomocysteinemia, increased bone resorption by osteoclasts may contribute to osteoporosis, and that an antioxidant may attenuate bone loss in these individuals.
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| Key Words:
Homocysteine, Osteoclasts, Oxidative stress, Antioxidants, Bone resorption |
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