Skeletal bone morphogenetic proteins suppress the expression of collagenase-3 by rat osteoblasts

Bone morphogenetic proteins (BMPs) are secreted by skeletal cells, induce the differentiation of mesenchymal cells into cells of the osteoblastic lineage, and increase their differentiated function. BMPs also decrease collagenase-3 expression by the osteoblast. We tested the autocrine role of BMPs on collagenase-3 expression in osteoblast-enriched cells from fetal rat calvariae (Ob cells) by examining the effects of noggin, a specific inhibitor of BMP binding and function. Although collagenase-3 transcript expression declined in untreated Ob cells in culture over a 24-h period, BMP-2, -4, and -6 decreased collagenase-3 messenger RNA levels in cells treated for 2-24 h. The addition of noggin prevented the decrease of collagenase-3 transcripts in control cultures, opposed the inhibitory actions of BMP-2, and increased the levels of the protease in the culture medium. Noggin did not alter the decay of collagenase-3 messenger RNA in transcriptionally arrested cells, and it increased the levels of collagenase-3 heterogeneous nuclear RNA in Ob cells. In conclusion, noggin enhances the synthesis of collagenase-3 in osteoblasts, supporting the notion that BMPs act as autocrine suppressors of collagenase-3 in skeletal cells, an effect that may contribute to the maintenance of the bone matrix.