AIMS AND BACKGROUND Osteosarcoma is the most common primary bone malignancy. Many genetic markers have proven prognostic value in osteosarcoma and studies are under way to determine their potential application as specific therapeutic targets. Runx2, Indian hedgehog (IHH), and Sox9 are proteins that play major roles in bone formation and tumorigenesis. We studied the protein expression of Runx2,...

The nuclear matrix (NM) is a fibrogranular network of ribonucleoproteins upon which transcriptional complexes and regulatory genomic sequences are organized. A hallmark of cancer is the disorganization of nuclear architecture; however, the extent to which the NM is involved in malignancy is not well studied. The RUNX1 and RUNX2 proteins form complexes within the NM to promote hematopoiesis and ...

BACKGROUND Numerous transcription factors are involved in the establishment and maintenance of the osteoblastic phenotype, such as Runx2, osterix and Dlx5. The transcription factor retinoblastoma binding protein-1 (RBP1) was recently identified as an estrogen regulated gene in an osteosarcoma cell model. Since the function of RBP1 in osteoblastic differentiation and mineralization is unknown, w...

Steroid hormones including (1,25)-dihydroxyvitamin D3, estrogens, and glucocorticoids control bone development and homeostasis. We show here that the osteogenic transcription factor Runx2 controls genes involved in sterol/steroid metabolism, including Cyp11a1, Cyp39a1, Cyp51, Lss, and Dhcr7 in murine osteoprogenitor cells. Cyp11a1 (P450scc) encodes an approximately 55-kDa mitochondrial enzyme t...

Purpose: To investigate the effect of miR-595 on osteogenic differentiation bone marrow mesenchymal stem cells (BMSCs).Methods: Human BMSCs were osteogenically differentiated, and protein expression alkaline phosphatase (ALP), osteocalcin (OCN), Runt-related transcription factor 2 (RUNX2) evaluated by western blot. Expression was measured quantitative reverse (qRT-PCR). The viability determined...

MicroRNAs (miRNAs) are small endogenous noncoding RNAs that play an instrumental role in post-transcriptional modulation of gene expression. Genes related to osteogenesis (i.e., RUNX2, COL1A1 and OSX) is important in controlling the differentiation of mesenchymal stem cells (MSCs) to bone tissues. The regulated expression level of miRNAs is critically important for the differentiation of MSCs t...

In the growth plate, the interplay between parathyroid hormone-related peptide (PTHrP) and Indian hedgehog (Ihh) signaling tightly regulates chondrocyte proliferation and differentiation during longitudinal bone growth. We found that PTHrP increases the expression of Zfp521, a zinc finger transcriptional coregulator, in prehypertrophic chondrocytes. Mice with chondrocyte-targeted deletion of Zf...

RESULTS: Inhibition of the BMPR signaling pathway inhibited Runx2 and BSPII gene expression of primary human mesenchymal stem cells (hMSCs) on MC-GAG. In contrast, inhibition of the MEK/ERK axis downregulated BSPII expression on Col-GAG independent of Runx2 expression. While inhibition of the BMPR signaling pathway resulted in decreased mineralization on both Col-GAG and MC-GAG, inhibition of t...

We have recently shown that a 150-bp Col10a1 distal promoter (-4296 to -4147 bp) is sufficient to direct hypertrophic chondrocyte-specific reporter (LacZ) expression in vivo. More recently, through detailed sequence analysis we identified two putative tandem-repeat Runx2 binding sites within the 3'-end of this 150-bp region (TGTGGG-TGTGGC, -4187 to -4176 bp). Candidate electrophoretic mobility ...

PC-1 is an enzymatic generator of pyrophosphate and a critical regulator of tissue mineralization. We previously showed that fibroblast growth factor-2 (FGF2) specifically induces PC-1 expression in calvarial pre-osteoblasts and that this occurs via a transcriptional mechanism involving Runx2. Because aberrant FGF signaling and Msx2 activity result in similar craniofacial skeletal defects and b...