2005 Fiscal Year Final Research Report Summary
ROLE OF RANKL IN OSTEOLYTIC BONE METASTASIS
| Project/Area Number |
16590313
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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 |
Experimental pathology
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| Research Institution | Kobe University |
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Principal Investigator |
KITAZAWA Riko Kobe University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 講師 (00273780)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Bone metastasis / Osteoclast / RANKL / Gene promoter / Gene transcription / PTHrP / Runx2 / CpG methylation |
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| Research Abstract |
Osteoclast differentiation factor (RANKL) is requisite for osteoclasts differentiation from hematopoietic precursors. To elucidate the mechanism of osteolytic bone metastasis, we assessed RANKL gene expression and osteoclastogenesis in mouse experimental model and human bone specimen. In both mouse and human osteolytic lesion due to cancer metastasis, RANKL expression was observed on the stromal/osteoblastic cells close to the cancer cell nests.
The effect of DNA methylation on its mRNA expression and osteoclastogenesis was analyzed. Subpopulations of ST2 cells were used : P9 which expresses RANKL and P16 which does not. CpG methylation of the -65/+350 region of the RANKL gene promoter, especially 3 bases upstream of TATA-box, was higher in P16 than in P9. In vitro methylation of the promoter construct reduced the transcriptional activity,5-aza-dC treatment recovered RANKL expression of P16 cells. Methylation of the RANKL gene promoter suppresses RANKL gene expression. The heterogeneity of osteoblastic cells in response to bone-resorbing stimuli may be attributed to the methylation status of the RANKL gene promoter.
We then analyzed the RANKL gene regulation by Runx2,transcrition factor essential for osteoblastic differentiation. We analyzed ST2 cells and Runx2 null mouse-derived C6 cells by RT-PCR,ChIP assay, and siRNA silencing. Runx2 suppresses the steady-state RANKL gene expression by condensing chromatin, while showing a slightly positive effect on RANKL basic promoter.
We have presented our data at various international as well as domestic meetings, and published scientific papers for academic journals.
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[Journal Article] Estimation of Contrast of Refraction Contrast Imaging Compared with Absorption Imaging -Basic Approach.2005
Author(s)
Hirano M, Yamasaki K, Okada H, Kitazawa S, Kitazawa R, Ohno Y, Sakurai T, Kondoh T, Ohbayashi C, Katafuchi T, _Maeda S, Sugimura K, Tamura S.
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Journal Title
Radiat Med 23
Pages: 89-96
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Dominant negative N-cadherin inhibit osteoclast diiferentiatio in by interfering with b-catenin regulation of RANKL, independent of cell-cell adhesion.2005
Author(s)
Shin CS, Her SJ, Kim JA, Kim DH, Kim SW, Kim HC, Park KH, Kim JG, Kitazawa R, Cheng SL, Civitelli R.
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Journal Title
J Bone Miner Res 20
Pages: 2200-2212
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Ray tracing analysis of overlapping objects in refraction contrast imaging.2005
Author(s)
Hirano M, Yamasaki K, Okada H, Sakurai T, Kondoh T, Karafuchi T, Sugimura K, Kitazawa S, Kitazawa R, Maeda S, Tamura S.
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Journal Title
Radiat Med 23
Pages: 386-389
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A case of MEN type I and menin in parathyroid lesions.2005
Author(s)
Tobimatsu T, Kaji H, Naito J, Yo M, Sowa H, Yamauchi M, Tsukada T, Kitazawa R, Kitazawa S, Sugimoto T, Chihara K.
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Journal Title
Nippon Naibunpitu Gakkai Zassi 81
Pages: 101-103
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Imaging of fine structure of bone sample with high coherence X-ray beam and high spatial resolution detector.2004
Author(s)
Hirano M, Yamasaki K, Kitazawa R, Kitazawa S, Okada H, Katafuchi T, Maeda S, Sakurai T, Kondoh T, Obayashi C, Sugimura K, Tamura S.
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Journal Title
Radiat Med 22
Pages: 56-59
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity.
Author(s)
Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, Kasga M.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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