A study on the molecular mechanism ofcytokine-mediated inhibition of osteoblast differentiation in rheumatoid arthritis
| Project/Area Number |
20591178
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Aichi Medical University |
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Principal Investigator |
YAMAMURA Masahiro Aichi Medical University, 医学部, 教授 (80252956)
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| Co-Investigator(Kenkyū-buntansha) |
向井 知之 愛知医科大学, 医学部, 助教 (00454421)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 関節リウマチ / 骨芽細胞 / 炎症性サイトカイン / 骨形成蛋白質 / 腫瘍壊死因子 / Smad / 骨形成タンパク質 |
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| Research Abstract |
The cellular mechanism for cytokine-mediated inhibition of BMP-induced osteoblastic differentiation was investigated using mouse myoblast C2C12 cells. Osteoblast transformation of BMP-cultured C2C12 cells, and their Runx2/osteocalcin expression, ALP activity, and parathyroid hormone (PTH) responsiveness (cAMP production) were inhibited by TNF-α, but not by IL-1, IL-6, or IL-17. BMP-induced Smad1, 5, 8 phosphorylation in the cells was suppressed by TNF-α signaling, but inhibitory Smad6 gene activation was increased as determined by cDNA array. MAP kinase analysis showed that ERK1/ERK2 and SAPK/JNK phosphorylation were selectively activated in the cells with TNF-α. BMPs had no effect on TNF type 1 and 2 receptor-expression. Notably, SAPK/JNK inhibitors restored TNF-α inhibition of osteoblast differentiation, as demonstrated by Id-1-promoter activity as well as Runx2/osteocalcin mRNA levels. These results suggest that TNF-α may have a crucial role in BMP-induced osteogenic inhibition in the diseases such as rheumatoid arthritis, through its SAPK/JNK activation and Smad6 induction.
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] Effect of infliximab on tumor necrosis factor-alpha-induced alterations in retinal microvascular endothelial cells and retinal pigment epithelial cells.2010
Author(s)
Li H, Yoneda M, Takeyama M, Sugita I, Tsunekawa H, Yamada H, Watanabe D, Mukai T, Yamamura M, Iwaki M, Zako M.
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Journal Title
J Ocul Pharmacol Ther 26(6)
Pages: 549-556
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