| Literature DB >> 24209761 |
Haiyan Qin1, Cunye Qu, Takayoshi Yamaza, Ruili Yang, Xia Lin, Xue-Yan Duan, Kentaro Akiyama, Yi Liu, Qunzhou Zhang, Chider Chen, Yibu Chen, Hank Heng Qi, Xin-Hua Feng, Anh D Le, Songtao Shi.
Abstract
Abnormal stem cell function makes a known contribution to many malignant tumors, but the role of stem cells in benign tumors is not well understood. Here, we show that ossifying fibroma (OF) contains a stem cell population that resembles mesenchymal stem cells (OFMSCs) and is capable of generating OF-like tumor xenografts. Mechanistically, OFMSCs show enhanced TGF-β signaling that induces aberrant proliferation and deficient osteogenesis via Notch and BMP signaling pathways, respectively. The elevated TGF-β activity is tightly regulated by JHDM1D-mediated epigenetic regulation of thrombospondin-1 (TSP1), forming a JHDM1D/TSP1/TGF-β/SMAD3 autocrine loop. Inhibition of TGF-β signaling in OFMSCs can rescue their abnormal osteogenic differentiation and elevated proliferation rate. Furthermore, chronic activation of TGF-β can convert normal MSCs into OF-like MSCs via establishment of this JHDM1D/TSP1/TGF-β/SMAD3 autocrine loop. These results reveal that epigenetic regulation of TGF-β signaling in MSCs governs the benign tumor phenotype in OF and highlight TGF-β signaling as a candidate therapeutic target.Entities:
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Year: 2013 PMID： 24209761 PMCID： PMC3861239 DOI： 10.1016/j.stem.2013.08.010
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633