BONE MORPHOGENETIC PROTEIN-2 TRANSIENTLY ENHANCES EXPRESSION OF A GENE, ID (INHIBITOR OF DIFFERENTIATION), ENCODING A HELIX-LOOP-HELIX MOLECULE IN OSTEOBLAST-LIKE CELLS

Bone morphogenetic protein 2 (BMP-2) is a potent inducer of differentiation of osteoblasts both in vivo and in vitro. We examined the action of BMP-2 on expression of a helix-loop-helix-type transcription factor, Id (inhibitor of differentiation), in osteoblast-like cells, as well as in osteoblast-enriched cells and possible precursor cells. To our surprise, BMP-2 enhanced Id gene expression in the cell types of osteoblastic lineage we examined. The maximal BMP-2 enhancement was observed within 24 hr in early proliferating cultures and the enhancement lasted up to % hr. The BMP-2 effect was not blocked by actinomycin D, while it was blocked by cycloheximide, suggesting that BMP-2 regulates Id gene expression at least in part via posttranscriptional events, which require protein synthesis. Other experiments indicated that BMP-2 did not further enhance Id mRNA levels promoted by dexamethasone, while BMP-2 did not resume the Id mRNA levels suppressed by 1,25-dihydroxyvitamin D3. Similar BMP-2 enhancement of Id message expression was also observed in osteoblast-enriched fetal rat calvaria cells as well as C3H10T1/2 cells. These results indicate that BMP-2 enhances expression of Id in early cultures of osteoblastic cells and suggest that enhancement of Id expression may somehow be involved in the promotion of differentiation by this cytokine in these osteoblastic cells and in their precursor cells.