Korean J Bone Metab > Volume 8(1); 2001 > Article
Korean Journal of Bone Metabolism 2001;8(1):17-23.
Effect of Cytokine-Induced Nitric Oxide on Formation, Apoptosis, and Activity of Osteoclast
사이토카인에 의해 유도된 산화질소가 파골세포의 생성, 세포소멸 및 활성에 미치는 영향
박혜림,김정화1,박용구2,장재석3
한림대학교 의과대학 병리학교실, 아산생명과학연구소1, 경희대학교 의과대학 병리학교실2, 울산대학교 의과대학 서울중앙병원 정형외과3
Abstract
Purpose
Nitric oxide (NO) has been regarded as biological active substance to induce bone remodeling and regulation of osteoclast activity. In this study we examine whether NO affects the osteoclast differentiation, especially as a mediator of cytokine effects. Materials and Methods: Osteoclasts were generated in 8-day primary culture of mouse bone marrow cells and the effect of NO donor and cytokine-induced NO on osteoclast formation was determined.
Results
SNP, a donor of NO, markedly enhanced NO production and inhibited 1,25-(OH)2D3 induced osteoclast generation compared to control. The addition of NO synthase inhibitor, L-NMMA with SNP attenuated these effects. The NO-mediated inhibition of osteoclast formation was not much related with apoptosis affecting mature osteoclasts. Stimulation of the culture with IL-1, TNF-, and IFN- enhanced NO production and these effects of cytokines were blocked by L-NMMA. TNF- and IFN- decreased osteoclast generation compared to control, but IL-1 increased it.
Conclusion
These findings suggest that the modulation of NOS and NO levels by cells within the bone microenvironment may be a sensitive mechanism for local control of osteoclast bone resorption. NO may be involved as a mediator of bone disease in conditions associated with cytokine activation.
Key Words: Osteoclast, Nitric oxide, Cytokine, Apoptosis
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