Abstract
Giant cell tumor of bone (GCT) is an aggressive tumor consisting of multinucleated osteoclast-like giant cells and proliferating osteoblast-like stromal cells. Our group has reported that the stromal cells express high levels of the bone resorbing matrix metalloproteinase (MMP)-13, and that this expression is regulated by the osteoblast transcription factor Runx2. The purpose of this study was to determine the upstream regulation of Runx2 in GCT cells. Using GCT stromal cells obtained from patient specimens, we demonstrated that TWIST, a master osteogenic regulator, was highly expressed in all GCT specimens. TWIST overexpression downregulated Runx2 expression whereas TWIST siRNA knockdown resulted in Runx2 and MMP-13 upregulation. Interestingly, cells obtained from a GCT lung metastasis showed a reverse regulatory pattern between TWIST and Runx2. In mutational analysis, we revealed a point mutation (R154S) at the Helix2 domain of TWIST. This TWIST mutation may be an essential underlying factor in the development and pathophysiology of these tumors in that they lead to inappropriate TWIST downregulation of Runx2, arrested osteoblastic differentiation, and the maintenance of an immature and neoplastic phenotype.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
