Dataset Information

The Sox2 high mobility group transcription factor inhibits mature osteoblast function in transgenic mice.

ABSTRACT: We have previously shown that in osteoblasts Sox2 expression can be induced by Fgfs, and can inhibit Wnt signaling and differentiation. Furthermore, in mice in which Sox2 is conditionally deleted in the osteoblastic lineage, bones are osteopenic, and Sox2 inactivation in cultured osteoblasts leads to a loss of proliferative ability with a senescent phenotype. To help understand the role of Sox2 in osteoblast development we have specifically expressed Sox2 in bone from a Col1?1 promoter, which extended Sox2 expression into more mature osteoblasts. In long bones, trabecular cartilage remodeling was delayed and the transition from endochondral to cortical bone was disrupted, resulting in porous and undermineralized cortical bone. Collagen deposition was disorganized, and patterns of osteoclast activity were altered. Calvarial bones were thinner and parietal bones failed to develop the diploic space. Microarray analysis showed significant up- or downregulation of a variety of genes coding for non-collagenous extracellular matrix proteins, with a number of genes typical of mature osteoblasts being downregulated. Our results position Sox2 as a negative regulator of osteoblast maturation in vivo.

SUBMITTER: Holmes G

PROVIDER: S-EPMC3167013 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Sox2 high mobility group transcription factor inhibits mature osteoblast function in transgenic mice.

Holmes Greg G Bromage Timothy G TG Basilico Claudio C

Bone 20110615 4

We have previously shown that in osteoblasts Sox2 expression can be induced by Fgfs, and can inhibit Wnt signaling and differentiation. Furthermore, in mice in which Sox2 is conditionally deleted in the osteoblastic lineage, bones are osteopenic, and Sox2 inactivation in cultured osteoblasts leads to a loss of proliferative ability with a senescent phenotype. To help understand the role of Sox2 in osteoblast development we have specifically expressed Sox2 in bone from a Col1α1 promoter, which ex ...[more]

PMID: 21703370

Similar Datasets

Project description:Root bark of Dictamnus dasycarpus Turcz. has been widely used as a traditional medicine and is a well-known anti-inflammatory agent. We isolated limonoid triterpene, obacunone (Obac) from the dried root bark of D. dasycarpus. Obac has been reported to exhibit varieties of biological activities including anti-inflammatory, anti-cancer, and anti-oxidant effects. This study aimed to investigate the beneficial effects and biological mechanisms of Obac in osteoblast differentiation and bone matrix mineralization. In the present study, Obac at concentrations ranging from 1 to 100 μM showed no proliferation effects in MC3T3-E1. The treatment of Obac (1 and 10 μM) increased wound healing and migration rates in a dose-dependent manner. Alkaline phosphatase (ALP) staining and activity showed that Obac (1 and 10 μM) enhanced early osteoblast differentiation in a dose-dependent manner. Obac also increased late osteoblast differentiation in a dose-dependent manner, as indicated by the mineralized nodule formation of ARS staining. The effects of Obac on osteoblast differentiation was validated by the levels of mRNAs encoding the bone differentiation markers, including Alp, bone sialoprotein (Bsp), osteopontin (Opn), and osteocalcin (Ocn). Obac increased the expression of bone morphogenetic protein (BMP), and the phosphorylation of smad1/5/8, and the expression of runt-related transcription factor 2 (RUNX2); Obac also inhibited GSK3β and upregulated the protein level of β-catenin in a dose-dependent manner during osteoblast differentiation. Obac-mediated osteoblast differentiation was attenuated by a BMP2 inhibitor, Noggin and a Wnt/β-catenin inhibitor, Dickkopf-1 (Dkk1) with the abolishment of RUNX2 expression and nuclear accumulation by Obac. Taken together, the findings of this study demonstrate that Obac has pharmacological and biological activates to promote osteoblast differentiation and bone mineralization through BMP2, β-catenin, and RUNX2 pathways, and suggest that Obac might be a therapeutic effect for the treatment and prevention of bone diseases such as osteoporosis and periodontitis.

Project description:During the last several decades, a number of transgenic or genetically modified tree varieties with enhanced characteristics and new traits have been produced. These trees have become associated with generally unsubstantiated concerns over health and environmental safety. We conducted transcriptome sequencing of transgenic Populus alba × P. berolinensis expressing the transcription factor JERF36 gene (ABJ01) and the non-transgenic progenitor line (9#) to compare the transcriptional changes in the apical buds. We found that 0.77% and 1.31% of the total expressed genes were significant differentially expressed in ABJ01 at the Daqing and Qiqihar sites, respectively. Among them, 30%-50% of the DEGs contained cis-elements recognized by JERF36. Approximately 5% of the total number of expressed genes showed significant differential expression between Daqing and Qiqihar in both ABJ01 and 9#. 10 DEGs resulting from foreign gene introduction, 394 DEGs that resulted solely from the environmental differences, and 47 DEGs that resulted from the combination of foreign gene introduction and the environment were identified. The number of DEGs resulting from environmental factors was significantly greater than that resulting from foreign gene introduction, and the combined effect of the environmental effects with foreign gene introduction was significantly greater than resulting from the introduction of JERF36 alone. GO and KEGG annotation showed that the DEGs mainly participate in the photosynthesis, oxidative phosphorylation, plant hormone signaling, ribosome, endocytosis, and plant-pathogen interaction pathways, which play important roles in the responses to biotic and abiotic stresses ins plant. To enhance its adaptability to salt-alkali stress, the transgenic poplar line may regulate the expression of genes that participate in the photosynthesis, oxidative phosphorylation, MAPK, and plant hormone signaling pathways. The crosstalk between biotic and abiotic stress responses by plant hormones may improve the ability of both transgenic and non-transgenic poplars to defend against pathogens. The results of our study provide a basis for further studies on the molecular mechanisms behind improved stress resistance and the unexpected effects of transgenic gene expression in poplars, which will be significant for improving the biosafety evaluation of transgenic trees and accelerating the breeding of new varieties of forest trees resistant to environmental stresses.

Dataset Information

The Sox2 high mobility group transcription factor inhibits mature osteoblast function in transgenic mice.

Publications

The Sox2 high mobility group transcription factor inhibits mature osteoblast function in transgenic mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets