objective: zoledronic acid as a main treatment for osteoporosis has an important role in differentiation of mesenchymal stem cells. however, mechanism of osteoblastic differentiation induction by zoledronic acid is not well understood until now. in this research we evaluate zoledronic acid effect on methylation status of runx2 and dlx5 promoters. materials and methods: after isolation and expa...

Src/Yes tyrosine kinase signaling contributes to the regulation of bone homeostasis and inhibits osteoblast activity. Here we show that the endogenous Yes-associated protein (YAP), a mediator of Src/Yes signaling, interacts with the native Runx2 protein, an osteoblast-related transcription factor, and suppresses Runx2 transcriptional activity in a dose-dependent manner. Runx2, through its PY mo...

BACKGROUND Cleidocranial dysplasia is a rare hereditary skeletal disorder due to heterozygous loss of function mutations in the RUNX2 gene that encodes runt-related transcription factor 2 (RUNX2). Here we report a 52 year-old woman with cleidocranial dysplasia due to a novel RUNX2 mutation. CASE DESCRIPTION A 52 year-old Han Chinese woman presented with short stature and skeletal dysplasia th...

Key components of DNA replication and the basal transcriptional machinery as well as several tissue-specific transcription factors are compartmentalized in specialized nuclear domains. In the present study, we show that determinants of subnuclear targeting of the bone-related Runx2/Cbfa1 protein reside in the C-terminus. With a panel of C-terminal mutations, we further demonstrate that targetin...

Ossification of the Posterior Longitudinal Ligament (OPLL) is a disease that is characterized by the ectopic calcification of the ligament; however, the pathogenesis of OPLL remains to be investigated. We attempted to identify the in vivo role of Runx2, a master regulator of osteoblast differentiation and skeletal mineralization, in the pathogenesis of OPLL. The expression of Runx2 in the ligam...

The Runx2/Cbfa1 transcription factor regulates a program of gene expression necessary for skeletal development. To understand signals mediating skeletal formation, we examined the in vivo spatio-temporal activity of the Runx2 P1 promoter which controls expression of the bone-related Type II isoform. Transgenic mice carrying 3 kb of Runx2 promoter fused to the lacZ gene exhibit localized promote...

Comparisons of the genomes of Neandertals and Denisovans with present-day human genomes have suggested that the gene RUNX2, which encodes a transcription factor, may have been positively selected during early human evolution. Here, we overexpress RUNX2 in ten human cell lines and identify genes that are directly or indirectly affected by RUNX2 expression. We find a number of genes not previousl...

Several homeodomain (HD) proteins are critical for skeletal patterning and respond directly to BMP2 as an early step in bone formation. RUNX2, the earliest transcription factor proven essential for commitment to osteoblastogenesis, is also expressed in response to BMP2. However, there is a gap in our knowledge of the regulatory cascade from BMP2 signaling to the onset of osteogenesis. Here we s...

Osteosarcoma (OS) is the most common bone cancer in children and young adults. The etiology of osteosarcoma is currently unknown. Besides the predominant osteoblasts, the presence of cartilage forming chondrocytes within its tumor tissues suggests a role of chondrogenesis in osteosarcoma development. Runx2 is a master transcription factor both for osteoblast differentiation and for chondrocyte ...

Changes to androgen signaling during prostate carcinogenesis are associated with both inhibition of cellular differentiation and promotion of malignant phenotypes. The androgen receptor (AR)-binding transcription factor RUNX2 has been linked to prostate cancer progression but the underlying mechanisms have not been fully defined. In this study, we investigated the genome-wide influence of RUNX2...