Regulators of differentiated cell fate can offer targets for managing cancer development and progression. Here, we identify Runx2 as a new regulator of epithelial cell fate in mammary gland development and breast cancer. Runx2 is expressed in the epithelium of pregnant mice in a strict temporally and hormonally regulated manner. During pregnancy, Runx2 genetic deletion impaired alveolar differe...

Intratumoral heterogeneity and treatment resistance drive breast cancer (BC) metastasis and recurrence. The RUNX2 transcription factor is upregulated in early stage luminal BC. However, the precise mechanism by which RUNX2 regulates an oncogenic phenotype in luminal BCs remains an enigma. We show that RUNX2 is predictive of poor overall survival in BC patients. RUNX2 associated with the TAZ tra...

Hyperglycemic conditions in diabetic patients can affect various cellular functions, including the modulation of osteogenic differentiation. However, the molecular mechanisms by which hyperglycemia affects osteogenic differentiation are yet to be clarified. This study aimed to investigate whether the aberrant increase in protein O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation) con...

Transforming growth factor-beta (TGF-beta) inhibits osteoblast differentiation through inhibition of the function of Runx2 (Cbfa1) by Smad3. The mechanism through which TGF-beta/Smad3 inhibits Runx2 function has not been characterized. We show that TGF-beta induces histone deacetylation, primarily of histone H4, at the osteocalcin promoter, which is repressed by TGF-beta, and that histone deace...

Activation of SIRT1 has previously been shown to protect mice against osteoporosis through yet ill-defined mechanisms. In this study, we outline a role for SIRT1 as a positive regulator of the master osteoblast transcription factor, RUNX2. We find that ex vivo deletion of sirt1 leads to decreased expression of runx2 downstream targets, but not runx2 itself, along with reduced osteoblast differe...

Although both osteoblasts and adipocytes have a common origin, i.e., mesenchymal cells, the molecular mechanisms that define the direction of two different lineages are presently unknown. In this study, we investigated the role of a transcription factor, CCAAT/enhancer binding protein beta (C/EBPbeta), and its isoform in the regulation of balance between osteoblast and adipocyte differentiation...

Reptiles have achieved highly diverse morphological and physiological traits that allow them to exploit various ecological niches and resources. Morphology of the temporal region of the reptilian skull is highly diverse and historically it has been treated as an important character for classifying reptiles and has helped us understand the ecology and physiology of each species. However, the dev...

Cleidocranial dysplasia (CCD) is a rare, well-defined skeletal disorder with autosomal dominant inheritance and complete penetrance. Although it involves the whole skeletal system, the main clinical manifestations of CCD are malformations of the skull and clavicles, which lead to a typical appearance of the face and shoulders. Dental aspects are particularly evident and often eruption difficult...

Insulin-like growth factor-1 (IGF-1) is an angiogenic and oncogenic factor that activates signal transduction pathways involved in the expression of transcriptional regulators of tumorigenesis. RUNX2, a member of the Ig-loop family of transcription factors is expressed in vascular endothelial cells (EC) and regulates EC migration, invasion, and proliferation. Here we show that IGF-1 and its rec...