Background. Members of the Runx gene family encode transcription factors that bind to DNA in a sequence-specific manner. Among the three Runx proteins, Runx2 comprises 607 amino acid (aa) residues, is expressed in bone, and plays crucial roles in osteoblast differentiation and bone development. We examined whether the Runx2 gene is also expressed in testes. Methods. Murine testes from 1-, 2-, 3...

RUNX2, a key transcription factor for osteoblast differentiation, is regulated by ERK1/2 and p38 MAP kinase-mediated phosphorylation. However, the specific contribution of each kinase to RUNX2-dependent transcription is not known. Here we investigate ERK and p38 regulation of RUNX2 using a unique P-RUNX2-specific antibody. Both MAP kinases stimulated RUNX2 Ser319 phosphorylation and transcripti...

How lineage specifiers are regulated during development is an outstanding question, and the molecular regulation of osteogenic factor RUNX2 remains to be fully understood. Here we report that the Mediator subunit MED23 cooperates with RUNX2 to regulate osteoblast differentiation and bone development. Med23 deletion in mesenchymal stem cells or osteoblast precursors results in multiple bone defe...

Cleidocranial dysplasia (CCD) is an autosomal dominant disorder caused by haploinsufficiency of the RUNX2 gene. In this study, we analyzed by direct sequencing RUNX2 mutations from eleven CCD patients. Four of seven mutations were novel: two nonsense mutations resulted in a translational stop at codon 50 (Q50X) and 112 (E112X); a missense mutation converted arginine to glycine at codon 131 (R13...

Runx2, a member of the family of runt-related transcription factors, is rhythmically expressed in bone and may be involved in circadian rhythms in bone homeostasis and osteogenesis. Runx2 is also expressed in the brain, but its function is unknown. We tested the hypothesis that in the brain, Runx2 may interact with clock-controlled genes to regulate circadian rhythms in behavior. First, we demo...

Understanding the regulation of endothelial cell (EC) gene expression has important implications for angiogenesis, tumor growth, and metastasis. The transcription factor runt-related gene 2 (RUNX2)/core binding factoralpha-1/acute myeloid leukemia 3/polyoma enhancer-binding protein 2alphaA/osteoblast-specific transcription factor 2 regulates osteoblast differentiation, increases lymphomagenesis...

Objective: Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia which is characterized by cranial, clavicular, and dental anomalies. Aberrations in the RUNX2 gene, which is considered to be responsible for CCD, were investigated in a Chinese family with CCD in this study. Methods: Genomic DNA was isolated from the blood samples of all 11 participants, including 3 patien...

The Runx2 (CBFA1/AML3/PEBP2alphaA) transcription factor promotes skeletal cell differentiation, but it also has a novel cell growth regulatory activity in osteoblasts. We addressed here whether Runx2 activity is functionally linked to cell cycle-related mechanisms that control normal osteoblast proliferation and differentiation. We found that the levels of Runx2 gene transcription, mRNA and pro...

The alpha1(X) collagen gene (Col10a1) is the only known hypertrophic chondrocyte-specific molecular marker. Until recently, few transcriptional factors specifying its tissue-specific expression have been identified. We show here that a 4-kb murine Col10a1 promoter can drive beta-galactosidase expression in lower hypertrophic chondrocytes in transgenic mice. Comparative genomic analysis revealed...

The ERK/MAP kinase pathway is an important regulator of gene expression and differentiation in postmitotic cells. To understand how this pathway controls gene expression in bone, we examined the subnuclear localization of P-ERK in differentiating osteoblasts. Induction of differentiation was accompanied by increased ERK phosphorylation and expression of osteoblast-related genes, including osteo...