@article{oai:nagasaki-u.repo.nii.ac.jp:00006659, author = {Shi, Xiuming and Deepak, Vishwa and Wang, Linghui and Ba, Xueqing and Komori, Toshihisa and Zeng, Xianlu and Liu, Wenguang}, issue = {7}, journal = {International Journal of Molecular Sciences}, month = {Jul}, note = {Thrombospondin-1 (TSP-1), a matricellular protein widely acclaimed to be involved in the inhibition of angiogenesis and tumorigenesis, is synthesized and secreted by many cell types, including osteoblast and cancer cells. TSP-1 is highly upregulated during early stage of osteogenesis, whereas it inhibits terminal osteoblast differentiation. Expression of TSP-1 is downregulated in cancer cells, and its ectopic expression has been shown to restrain tumor growth. Transcriptional regulation of TSP-1 in osteogenesis and cancer is poorly understood; this prompted us to study its regulation by the two key regulators of the aforementioned processes: Runx2 and Runx3. Through a PCR-based cDNA subtraction technique, we identified and cloned a cDNA fragment for mouse TSP-1, whose expression was dramatically upregulated in response to Runx2 expression in mesenchymal stem cells. Moreover, TSP-1 expression was considerably reduced in the lung of Runx2 knockout mouse. On the other hand, TSP-1 gene expression drastically increased at both the transcriptional and translational levels in response to Runx3 expression in B16-F10 melanoma cells. In line with this, Runx2 and Runx3 bound to the TSP-1 promoter and stimulated its activity. Hence, these results provide first line of evidence that TSP-1 is a transcriptional target gene of Runx2 and Runx3., International Journal of Molecular Sciences, 14(7), pp.14321-14332; 2013}, pages = {14321--14332}, title = {Thrombospondin-1 Is a Putative Target Gene of Runx2 and Runx3}, volume = {14}, year = {2013} }