کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2781903 1153337 2007 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Interleukin-10 inhibits RANKL-mediated expression of NFATc1 in part via suppression of c-Fos and c-Jun in RAW264.7 cells and mouse bone marrow cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی تکاملی
پیش نمایش صفحه اول مقاله
Interleukin-10 inhibits RANKL-mediated expression of NFATc1 in part via suppression of c-Fos and c-Jun in RAW264.7 cells and mouse bone marrow cells
چکیده انگلیسی

Interleukin-10 (IL-10), an anti-inflammatory cytokine, has been shown to inhibit osteoclast formation and bone resorption in rat and mouse systems. However, the precise intracellular mechanism(s) of this action remains unclear. The aim of this study was to clarify the role of IL-10 in the regulation of critical transcription factors involved in osteoclastogenesis. A RAW264.7 macrophage cell line, which constitutively expressed IL-10 receptor, was differentiated to osteoclasts with stimulation of receptor activator of nuclear factor κB ligand (RANKL). IL-10 inhibited the RANKL-induced osteoclastogenesis. IL-10 potently reduced the RANKL-induced expression of NFATc1, c-Jun and c-Fos, which are known to be essential for osteoclastogenesis, in time- and dose-dependent manners. The IL-10-induced inhibition of these transcription factors was observed in the system of mouse bone marrow precursors. Besides these transcription factors, IL-10 also decreased the RANKL-induced expression of NF-κB p50 and phosphorylation of JNK. To determine which signaling was critical for the IL-10 effect, we examined the effect of overexpression of NFATc1, c-Fos, and c-Jun on the IL-10-induced inhibition of osteoclastogenesis. As expected, overexpression of NFATc1 abrogated the IL-10-induced inhibition of osteoclastogenesis. Interestingly, overexpression of either c-Fos or c-Jun partially rescued the reduction of RANKL-induced expression of NFATc1 and osteoclastogenesis by IL-10. These data suggest that IL-10 may down-regulate osteoclastogenesis mainly through inhibition of the expression of NFATc1, c-Fos and c-Jun. These findings provide new insight into the inhibitory action of IL-10 on RANKL-mediated osteoclastogenesis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 41, Issue 4, October 2007, Pages 592–602
نویسندگان
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