新科学想法 › 文献管理 › 浏览文献

TNF Inhibits Mesenchymal Stem Cell Differentiation into Osteoblasts via the Ubiquitin E3 Ligase Wwp1

cnefs 添加于 2011-9-4 19:08 | 1210 次阅读 | 0 个评论

作者
Zhao L, Huang J, Zhang H, Wang Y, Matesic LE, Takahata M, Awad H, Chen D, Xing L
摘要
Patients with chronic inflammatory disorders, such as rheumatoid arthritis, often have osteoporosis due to a combination of TNF-induced increased bone resorption and reduced bone formation. To test if TNF inhibits bone formation by affecting the commitment and differentiation of mesenchymal stem cells (MSCs) into osteoblasts, we examined the osteogenic potential of MSCs from TNF transgenic (TNF-Tg) mice, a model of chronic inflammatory arthritis. MSC-enriched cells were isolated from bone marrow stromal cells using negative selection with anti-CD45 antibody coated magnetic beads. The expression profile of MSC surface markers the osteogenic, chondrogenic and adipogenic properties of CD45(-) cells were confirmed by FACS and cell differentiation assays. MSC-enriched CD45(-) cells from TNF-Tg mice formed significantly decreased numbers of fibroblast and ALP(+) colonies and had a decreased expression of osteoblast marker genes. Since TNF may up-regulate ubiquitin ligases which negatively regulate osteoblast differentiation, we examined the expression levels of several ubiquitin ligases and found that Wwp1 expression was significantly increased in MSC-enriched CD45(-) cells of TNF-Tg mice. Wwp1 knockdown rescued impaired osteoblast differentiation of TNF-Tg CD45(-) cells. Wwp1 promotes ubiquitination and degradation of JunB, an AP-1 transcription factor that positively regulates osteoblast differentiation. Injection of TNF into WT mice resulted in decreased osteoblast differentiation of MSCs and increased JunB ubiquitination, which was completely blocked in Wwp1(-/-) mice. Thus, Wwp1 targets JunB for ubiquitination and degradation in MSCs after chronic exposure to TNF, and inhibition of Wwp1 in MSCs could be a new mechanism to limit inflammation-mediated osteoporosis by promoting their differentiation into osteoblasts.
详细资料
- 文献种类:期刊
- 期刊名称: Stem Cells (Dayton, Ohio)
- 期刊缩写: Stem Cells
- 期卷页: 2011年
- 地址: Department of Pathology and Laboratory Medicine, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642
- 日期: 2011-8-1
- ISBN: 1066-5099
- 备注:PMID:21809421
标签

分化 TNF
相关链接 DOI URL
cnefs 的文献笔记订阅

TNF and MSC
??