The progressive ankylosis gene (ank) encodes a transmembrane protein that transports intracellular inorganic pyrophosphate (PP(i)) to the extracellular milieu. ank/ank mice, which express a truncated nonfunctional ANK, showed a markedly reduced bone mass, bone-formation rate, and number of tartrate-resistant acid phosphatase-positive (TRAP(+)) multinucleated osteoclasts. ANK function deficiency...

Runx2 is a Runt domain transcription factor that transcriptionally regulates osteoblast differentiation and bone formation. In this study, we show that human chondro- and osteosarcoma cell lines, human mesenchymal stem cells (hMSC) and a human primary chondrocytes (HC), osteoblst cells (HOb) express an intact isoform (RUNX2wt) and 3 alternatively spliced isoforms (RUNX2Delta5, Delta7, and Delta...

Two regulatory pathways, bone morphogenetic protein (BMP)/transforming growth factor-beta (TGFbeta) and the transcription factor RUNX2, are required for bone formation in vivo. Here we show the interdependent requirement of these pathways to induce an osteogenic program. A panel of Runx2 deletion and point mutants was used to examine RUNX2-SMAD protein-protein interaction and the biological con...

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...

Stage-specific expression of ameloblast-specific genes is controlled by differential expression of transcription factors. In addition, ameloblasts follow daily rhythms in their main activities (i.e. enamel protein secretion and enamel mineralization). This time-related control is orchestrated by oscillations of clock proteins involved in the regulation of circadian rhythms. Our aim was to ident...

To investigate the effects of Genistein on the osteogenic related gene expression profiles during osteoblastic differentiation of human bone marrow mesenchymal stem cell (hBMSC) cultures, the hBMSCs were cultured under osteogenic differentiation medium with the addition of Genistein (10(-8)∼10(-5) M) for 12 days. The cell proliferation was measured by BrdU incorporation, while the osteoblastic ...

Hedgehog and canonical Wnt/beta-catenin signaling are implicated in development of the osteoblast, the bone matrix-secreting cell of the vertebrate skeleton. We have used genetic approaches to dissect the roles of these pathways in specification of the osteoblast lineage. Previous studies indicate that Ihh signaling in the long bones is essential for initial specification of an osteoblast proge...

The orphan nuclear receptor small heterodimer partner (SHP; NR0B2) interacts with a diverse array of transcription factors and regulates a variety of cellular events such as cell proliferation, differentiation, and metabolism. However, the role of SHP in bone formation has not yet been elucidated. SHP expression is significantly increased during osteoblast differentiation, and its expression is...

BACKGROUND Ectopic ossification and increased vascularization are two common phenomena in the chronic tendinopathic tendon. The increased vascularization usually leads to an elevated local oxygen tension which is one of micro-environments that can influence differentiate status of stem cells. OBJECTIVE This study aimed to investigate the osteogenesis capacity of rat tendon-derived stem cells ...

NELL-1 is a novel secreted protein associated with premature fusion of cranial sutures in craniosynostosis that has been found to promote osteoblast cell differentiation and mineralization. Our previous study showed that Runx2, the key transcription factor in osteoblast differentiation, transactivates the NELL-1 promoter. In this study, we evaluated the regulatory involvement and mechanisms of ...