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 differenti ation of osteoblasts both in vivo and in vitro. We examined the action of BMP-2 on expression of a helix-loop-helix-type transcription facto r, Id (inhibitor of differentiation), in osteoblast-like cells, as wel l as in osteoblast-enriched cells and possible precursor cells. To our surprise, BMP-2 enhanced Id gene expression in the cell types of oste oblastic lineage we examined. The maximal BMP-2 enhancement was observ ed within 24 hr in early proliferating cultures and the enhancement la sted up to % hr. The BMP-2 effect was not blocked by actinomycin D, wh ile it was blocked by cycloheximide, suggesting that BMP-2 regulates I d gene expression at least in part via posttranscriptional events, whi ch require protein synthesis. Other experiments indicated that BMP-2 d id not further enhance Id mRNA levels promoted by dexamethasone, while BMP-2 did not resume the Id mRNA levels suppressed by 1,25-dihydroxyv itamin D3. Similar BMP-2 enhancement of Id message expression was also observed in osteoblast-enriched fetal rat calvaria cells as well as C 3H10T1/2 cells. These results indicate that BMP-2 enhances expression of Id in early cultures of osteoblastic cells and suggest that enhance ment of Id expression may somehow be involved in the promotion of diff erentiation by this cytokine in these osteoblastic cells and in their precursor cells.