Molecular biological studies on regulators of endochondral bone formation

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We purified membrane-bound transferrin-like protein (MTF=chondrotransferrin) and cloned cDNA encoding MTF.In addition, we determined the genomic structure of MTG including the 5' upstream promoter region. In the promoter region, there are several binding sites for transcriptiona1 factors involved in chondrocyte-specific gene expression including sox9. We also cloned mouse MTF cDNA, and found that MTF is diverged from the common ancestor gene earlier than the other members of the transferrin family. In cultures of chondrogenic cells, MTF expression was initiated after the onset of chondrogenic differentiation, and its expression level changed in parallel with those of type II collagen and aggrecan. MTF antisense oligomers suppressed chondrocyte differentlation. These findings suggest that in addition to transferrin, MTF plays an important role in chondrocyte differentiation.We also found that a C-terminal PTH fragment modulates the expression of osteopontin, type X collagen, MMPs, PTHrP and PTH receptor mRNA, and that retinol-binding protein is involved in mediating the action of PTH and PTHrp on chondrocytes during endochondral bone formation.