Disease relevance of Sp7

• Taken together, these results suggested that T-614 possessed anabolic effects on bone metabolism, besides suppressor of bone resorption, by increased expression of osterix [1].
• One of the proteins is the C22 component of alkyl hydroperoxide reductase, which is induced by hydrogen peroxide in Salmonella typhimurium [2].
• Expression of the Aop1 gene product in E. coli deficient in the C22-subunit gene rescued resistance of the bacteria to alkylhydroperoxide [3].
• The activity of the C22 compound was not due to toxicity, since transformation occurred in carcinogen-treated cultures after its removal; neither was it due to antiproliferative effects on transformed cells, since the C22 compound did not prevent focus formation by transformed cells in reconstruction experiments [4].

High impact information on Sp7

• TSH also inhibits osteoblast differentiation and type 1 collagen expression in a Runx-2- and osterix-independent manner by downregulating Wnt (LRP-5) and VEGF (Flk) signaling [5].
• In Osx null mice, no bone formation occurs [6].
• In endochondral skeletal elements of Osx null mice, mesenchymal cells, together with osteoclasts and blood vessels, invade the mineralized cartilage matrix [6].
• NFAT and Osterix cooperatively regulate bone formation [7].
• CIZ deficiency enhanced the levels of mRNA expression of genes encoding proteins related to osteoblastic phenotypes, such as alkaline phosphatase (ALP) as well as osterix mRNA expression in whole long bones [8].

Biological context of Sp7

• The enhancing effect of BMP on osterix gene expression was observed in a dose-dependent manner starting at 200 ng/ml [9].
• The expression of genes encoding osteocalcin and Cbfa1 was upregulated and the formation of mineralized bone nodules was significantly increased by osterix transfection [10].
• The finding that Osx-null cells acquire a chondrocyte phenotype implies that Osx is a negative regulator of Sox9 and of the chondrocyte phenotype [11].
• Analysis of the Osx promoter revealed two transcription start sites that direct the expression of an abundant mRNA (Osx1) and an alternatively spliced mRNA (Osx2) [12].
• This up-regulation was abrogated when the Runx2 responsive element on the Osx promoter was mutated [13].

Anatomical context of Sp7

• In Osx null mice osteoblast differentiation is impaired and bone formation is absent [14].
• In this study, we hypothesized that overexpression of Osx in murine bone marrow stromal cells (BMSC) would be able to enhance their osteoblastic differentiation and mineralization in vitro [14].
• Osterix enhances proliferation and osteogenic potential of bone marrow stromal cells [14].
• Because Osx null preosteoblasts express typical chondrocyte marker genes, we propose that Runx2/Cbfa1-expressing preosteoblasts are still bipotential cells [6].
• This suggests that the process of osterix-induced differentiation of ES cells involves transition through an intermediate bi- or tripotential progenitor cell population [10].

Associations of Sp7 with chemical compounds

• NFAT and Osterix form a complex that binds to DNA, and this interaction is important for the transcriptional activity of Osterix [7].
• The BMP enhancement of the osterix gene expression in chondrocytes was blocked in the presence of a protein synthesis inhibitor, cycloheximide, while it was still observed in the presence of 5,6-dichloro-1-beta D-ribofuranosylbenzimidazol (DRB) suggesting the involvement of post-transcriptional events, which require new protein synthesis [9].
• In this study, we have used a murine preosteoblast cell line MC3T3-E1 cells to demonstrate that DMSO effectively induces osteoblastic differentiation of MC3T3-E1 cells via the activation of Runx2 and osterix and is dependent upon the protein kinase C (PKC) pathways [15].
• We further analyzed the effects of continuous activation of Wnt signaling by lithium chloride and observed that osteoblast differentiation was reduced, as measured by expression of osteoblast marker genes encoding alkaline phosphatase, osteocalcin, and osterix, as well as by the amount of calcium release [16].
• We identified the transactivation domain of Osterix, which contains high proline and glycine residues and has an activation property in mammalian and yeast cells [17].

Regulatory relationships of Sp7

• Bone morphogenetic protein-2 enhances osterix gene expression in chondrocytes [9].
• Furthermore, a mutant in which the Osterix gene was inactivated in Sox9-expressing cells exhibited a lack of endochondral and intramembranous ossification and a lack of mature osteoblasts comparable with Osterix-null mutants [18].
• Reporter assays indicate that p53 represses osterix transcription by the minimal promoter in a DNA-binding-independent manner [19].
• These findings suggest that Osterix is regulated via both Runx2-dependent and -independent mechanisms, and that Osterix controls osteoblast differentiation, at least in part, by regulating the expression of genes not controlled by Runx2 [20].
• Third, Dlx5 overexpression and knock-down assays demonstrate its role in activating Osterix expression in response to BMP-2 [21].

Other interactions of Sp7

• Ectopic expression of MyoD increased alkaline phosphatase activity and Osterix mRNA expression in response to BMP treatment [22].
• Spaciotemporal association and bone morphogenetic protein regulation of sclerostin and osterix expression during embryonic osteogenesis [23].
• Thus, Osx acts downstream of Runx2/Cbfa1 [6].
• We therefore examined the effects of BMP-2 on osterix gene expression in chondrocytes in culture [9].
• Unlike other bone markers examined such as Osterix and type II collagen, OST transcripts do not appear to be expressed by chondrocytes of epiphyseal cartilage or by non-hypertrophic or hypertrophic chondrocytes [24].

Analytical, diagnostic and therapeutic context of Sp7

• RT-PCR analysis indicated that osterix mRNA was expressed in the primary cultures of chondrocytes derived from mouse rib cartilage [9].
• BMP effects on the osterix mRNA levels were also confirmed by Northern blot analysis [9].
• An in situ hybridization study of Runx2, Osterix, and Sox9 at the onset of condylar cartilage formation in fetal mouse mandible [25].
• Results: Before transplantation, PRP enhanced the expression of Osterix and bone sialoprotein mRNAs compared with PPP [26].
• We investigated the methylation status of Dlx5 and Osx in osteogenic and nonosteogenic cell lines by methylation-specific PCR (MSP) [27].

References