Disease relevance of SP7

• Chronic metabolic acidosis enhanced the messenger RNA (mRNA) and protein expression of early osteoblast transcription factor, runx-2, whereas inhibiting osterix and having no effect on ATF-4 [1].
• A strain of Spirillum lipoferum with intense red pigmentation was isolated from the roots of Cynodon dactylon "Coastal." This isolate vigorously reduced acetylene when grown in N-free, Na-malate, semisolid agar, and it was identical to S. lipoferum strain SP7 by standard taxonomic tests [2].
• We hypothesized that osterix might have a role in osteosarcoma tumor growth and metastasis [3].
• Osterix expression was also associated with decreased osteolysis [3].

High impact information on SP7

• The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation [4].
• Osterix, a transcription factor for osteoblast differentiation, mediates antitumor activity in murine osteosarcoma [3].
• Northern blot analysis showed that the mRNA level of osterix was decreased in two mouse osteosarcoma cell lines compared with its level in normal mouse osteoblasts [3].
• By studying Saos-2 cells, we showed that the transcription factors, Sp1, Sp3, and Sp7 (Osterix), regulate COL11A2 expression through its proximal promoter [5].
• Using high-density micromass cultures of mesenchymal cells as well as chondrocytes that had differentiated in vivo and were maintained in short-term monolayer culture, we demonstrate elevated Runx2, Osterix and Osteocalcin transcript levels in chondrocyte cultures upon inhibition of p38 activity with the pharmacological inhibitor PD169316 [6].

Biological context of SP7

• This inhibitory effect was connected to a reversible suppression of OSX gene expression and was specific to endothelial cells [7].
• The human SP7 cDNA encodes a putative 431 amino acid protein that contains three consecutive C2H2 zinc finger repeats [8].
• The SP7 gene consists of two exons, with exon 2 containing most of the protein coding sequence [8].
• RT-PCR revealed upregulation of the marker genes related to cell growth, differentiation, and mineralization, and BMP-2, osterix, and osteopontin were upregulated as a result [9].
• Runt-related transcription factor 2 (Runx2) and osterix are osteoblast-specific transcription factors essential for the development of osteoblastic cells and bone formation [10].

Anatomical context of SP7

• Human endothelial cells inhibit BMSC differentiation into mature osteoblasts in vitro by interfering with osterix expression [7].
• However, gene expression of osterix was not detected in dental follicle cells during osteogenic differentiation; this gene is expressed during osteogenic differentiation in bone marrow stem cells [11].
• The expression of a SP7 mRNA transcript of approximately 3.2 kb is restricted to bone-derived cell lines in vitro but undetectable in any adult tissues including mandibular bone by Northern blot hybridization [8].
• Continuous Dex treatment stimulated adipocyte formation, but failed to induce Osterix expression and mineralized matrix formation [12].
• Expression of preosteoblast markers and Cbfa-1 and Osterix gene transcripts in stromal tumour cells of giant cell tumour of bone [13].

Associations of SP7 with chemical compounds

• Both direct and collagen-mediated signals are required for active vitamin D3-elicited differentiation of human osteoblastic cells: roles of osterix, an osteoblast-related transcription factor [14].
• Moreover, pre-treatment of the cells with calphostin C, a PKC-specific inhibitor, reduced the increase in osterix transcripts enhanced by PTH and PMA 12 h after treatment [10].
• Forskolin, an adenylate cyclase activator, also enhanced Runx2 and osterix transcription, and the stimulatory effects of PTH and forskolin were blocked by the pre-treatment of the cells with H-89, a protein kinase A (PKA) inhibitor [10].
• Any tested concentration of gentamicin up to 800 mug/ml for 48 h did not inhibit or decrease the osteogenic gene expression of osterix and alkaline phosphatase of the C2C12 cells [15].
• Rosiglitazone had no effect on the number of early osteoblast or osteoclast progenitors, or on osteoblast life span, but decreased the expression of the key osteoblastogenic transcription factors Runx2 and Osterix in cultures of marrow-derived mesenchymal progenitors [16].

Regulatory relationships of SP7

• However, BMP-2 treatment of Dex-treated cells induced Osterix expression and subsequent mineralized matrix formation [12].
• Parathyroid hormone regulates osterix and expression predominantly through protein signaling in osteoblast-like cells [10].

Other interactions of SP7

• In cells grown under osteoblastic differentiation conditions, the expression of the osteoblastic markers osteocalcin, bone sialoprotein, osterix, and Runx2 and alkaline phosphatase activity was upregulated when incubated in air; however, it was blocked at low (3%) pO2 [17].
• We conclude that HUVEC can inhibit dexamethasone-induced BMSC differentiation into osteoblasts in vitro, by interfering with OSX expression, thereby arresting BMSC differentiation at a preosteoblastic stage [7].
• Purified PAPP-A protein directly up-regulated runt-related transcription factor 2 and Igf-I gene expression but not Osterix [18].
• SP1 and SP7 were used to induce anti-peptide antibodies in mouse and rabbit [19].
• RESULTS: The different surfaces did not alter the mRNA expression for ALP, type I collagen, osterix, osteocalcin, or BSP II [20].

Analytical, diagnostic and therapeutic context of SP7

• The specific expression of SP7 mRNA in osteoblasts in vivo was further confirmed by in situ hybridization on human embryonic tissues [8].
• Molecular cloning, structure, expression, and chromosomal localization of the human Osterix (SP7) gene [8].
• Real-time PCR analysis indicated that Cbfa-1, osterix and osteocalcin mRNA were present in primary cultures of GCTSC [13].
• In contrast, the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) had no effect on Runx2 transcription, but induced an increase in osterix mRNA level at the concentration of 500 nM at 12 h after treatment [10].
• Results: Before transplantation, PRP enhanced the expression of Osterix and bone sialoprotein mRNAs compared with PPP [21].

References