Noggin gene delivery inhibits cementoblast-induced mineralization.

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Abstract
Bone morphogenetic proteins (BMPs) are known to promote periodontal tissue regeneration, while noggin inhibits the biological activities of BMP-2, -4, and -7. To investigate the effect of BMPs and noggin gene transfer on cementogenesis, we used cloned murine cementoblasts (OCCM). Cells were transduced using adenoviruses encoding BMP-7 (Ad-BMP-7), noggin devoid of the heparin binding site (Ad-NOGΔ B2), or a control adenovirus encoding green fluorescent protein (Ad-GFP). Cells were seeded into 3D polymer scaffolds and implanted into SCID mice to determine the in vivo mineral-inducing ability of the cells. Cells transduced with Ad-NOGΔ B2 at 3 and 6 weeks postimplantation exhibited reduced mineral formation compared with all other groups. Although gene expression of osteocalcin and bone sialoprotein increased after Ad-BMP-7 transduction in vitro, following BMP-7 gene transfer in vivo, transcripts for OCN and BSP were not significantly different from controls, and mineral density was not significantly increased compared with Ad-GFP and NT groups. These results indicate that in mature cementoblast populations, gene transfer of noggin inhibits biomineralization induced by cementoblasts, whereas exogenous BMP has minimal effects on mineralization.