Abstract
The runt-related transcriptional factor RUNX2 is an essential mediator of the osteoblast phenotype and plays a pivotal role in the process of osteoblast differentiation. The involvement of RUNX2 includes the regulation of genes that are important in committing cells to the osteoblast lineage. Increasing evidences are consistent with a requirement of RUNX2 for stringent control of osteoblast proliferation and recent data even suggested that RUNX2 might act as a proapoptotic factor. Among the cytokines described as modulators of osteoblast functions, TNFα affects both apoptosis and the differentiation rate from mesenchymal precursor cells of osteoblast. Thus we evaluated on the human osteosarcoma cell line SaOs-2 stably transfected with a RUNX2 dominant negative construct (ΔRUNX2) the effects of serum and TNFα on proliferation and apoptosis. In this study we showed that SaOs-2 clones expressing high levels of ΔRUNX2 presented a higher proliferation rate than clones transfected with an empty vector. This increase in cell growth was accompanied by a rise in cyclins A1, B1 and E1 expression and a decrease in the cyclin inhibitor p21. Moreover we observed that the expression of the RUNX2 transgene protected the SaOs-2 cells from the antiproliferative and the apoptotic effects induced by TNFα. This was accompanied by the inhibition of Bax and activation of Bcl2 expression. Experiments done on SaOs-2 cells transiently transfected with siRNA confirmed that RUNX2 represents a critical link between cell fate, proliferation and growth control. This study also suggested that RUNX2 might control osteoblastic growth depending on the differentiation stage of the cells by regulating expression of elements involved in hormones and cytokines sensitivity.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: 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.