Abstract
BackgroundOsteogenic and chondrocytic differentiation involves a cascade of coordinated transcription factor gene expression that regulates proliferation and matrix protein formation in a defined temporo-spatial manner. Bone morphogenetic protein-2 induces expression of the murine Osterix/Specificity protein-7 (Sp7) transcription factor that is required for osteoblast differentiation and bone formation. Regulation of its expression may prove useful for mediating skeletal repair.ResultsSp7, the human homologue of the mouse Osterix gene, maps to 12q13.13, close to Sp1 and homeobox gene cluster-C. The first two exons of the 3-exon gene are alternatively spliced, encoding a 431-residue long protein isoform and an amino-terminus truncated 413-residue short protein isoform. The human Sp7 protein is a member of the Sp family having 78% identity with Sp1 in the three, Cys2-His2 type, DNA-binding zinc-fingers, but there is little homology elsewhere. The Sp7 mRNA was expressed in human foetal osteoblasts and craniofacial osteoblasts, chondrocytes and the osteosarcoma cell lines HOS and MG63, but was not detected in adult femoral osteoblasts. Generally, the expression of the short (or beta) protein isoform of Sp7 was much higher than the long (or alpha) protein isoform. No expression of either isoform was found in a panel of other cell types. However, in tissues, low levels of Sp7 were detected in testis, heart, brain, placenta, lung, pancreas, ovary and spleen.ConclusionsSp7 expression in humans is largely confined to osteoblasts and chondrocytes, both of which differentiate from the mesenchymal lineage. Of the two protein isoforms, the short isoform is most abundant.
Highlights
Osteogenic and chondrocytic differentiation involves a cascade of coordinated transcription factor gene expression that regulates proliferation and matrix protein formation in a defined temporo-spatial manner
To further elucidate the molecular basis of osteoblast-specific gene expression and differentiation we examined the sequence and expression of the human homologue of Osterix transcription factor, Specificity protein-7 (Sp7)
Sp7/Osterix was first identified by its induction in the murine pluripotent myoblast C2C12 cell line stimulated with bone morphogenetic protein-2 (BMP-2) and is upregulated in bone marrow stromal cells and chondrocytes [4,5,14]
Summary
Osteogenic and chondrocytic differentiation involves a cascade of coordinated transcription factor gene expression that regulates proliferation and matrix protein formation in a defined temporo-spatial manner. Osteoblasts express high levels of a number of extracellular matrix proteins such as type α1collagen, type α2(II) collagen, bone sialoprotein, osteopontin, fibronectin, and osteocalcin required for mineralization [6,7]. Control of their expression is regulated by a number of transcription factors such as runt-related transcription factor-2/core binding factor alpha subunit-1 (Runx2/Cbfa1) [7], Nmp4 [8], AJ18 [9,10]. In Sp7/Osterix null mice these Runx2/Cbfa positive preosteoblast cells do not deposit bone matrix and still express chondrocyte marker genes suggesting that they have the potential to develop into chondrocyte or osteoblasts. In bone marrow stromal cells from COX-2 knockout mice Osterix expression is reduced compared to wild-type mice and can be recovered by the addition of prostaglandin E2, indicating that COX-2 mediated skeletal repair involves Sp7/Osterix [4]
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