title: RUNX2 regulates the effects of TNFalpha on proliferation and apoptosis in SaOs-2 cells.
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, TNFalpha 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 (DeltaRUNX2) the effects of serum and TNFalpha on proliferation and apoptosis. In this study we showed that SaOs-2 clones expressing high levels of DeltaRUNX2 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 TNFalpha. 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.
authors.affiliation: LR2B/LBCM - EA 2603 - IFR 114. Université Lille Nord de France. Boulogne-sur-mer. France.
authors.forename: Ghali
authors.initials: G
authors.lastname: Olfa
authors.forename: Chauveau
authors.initials: C
authors.lastname: Christophe
authors.forename: Lencel
authors.initials: L
authors.lastname: Philippe
authors.forename: Salomez
authors.initials: S
authors.lastname: Romain
authors.forename: Hani
authors.initials: H
authors.lastname: Khaled
authors.forename: Hardouin
authors.initials: H
authors.lastname: Pierre
authors.forename: Broux
authors.initials: B
authors.lastname: Odile
authors.forename: Devedjian
authors.initials: D
authors.lastname: Jean-Christophe
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D034741:RNA, Small Interfering; C493709:RUNX2 protein, human; D014409:Tumor Necrosis Factor-alpha