TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL REGULATION OF INTERSTITIAL COLLAGENASE BY PLATELET-DERIVED GROWTH-FACTOR BB IN BONE CELL-CULTURES

Platelet-derived growth factor (PDGF), a bone cell mitogen, stimulates bone collagen degradation and does not enhance bone matrix apposition rates. The mechanism of the effect on collagen degradation is unknown , and it could involve changes in interstitial collagenase synthesis. We tested the effects of PDGF on interstitial collagenase expression i n cultures of osteoblast-enriched cells from fetal rat calvariae (Ob c ells). After 4-8 h of treatment, PDGF BE at 0.3 nM increased steady st ate collagenase messenger RNA (mRNA), whereas PDGF AA had no effect. T he effect of PDGF BE on collagenase transcripts was dose dependent. PD GF BE increased the levels of immunoreactive collagenase after 6 h, wh ereas the levels were decreased after 16 h. Stimulation of collagenase mRNA by PDGF BE was dependent on de novo protein synthesis and activa tion of protein kinase C. PDGF BE prolonged the half-life of collagena se mRNA in transcriptionally arrested cells. PDGF BE initially increas ed and subsequently decreased the rate of collagenase gene transcripti on and the levels of collagenase heterogeneous nuclear RNA. In conclus ion, PDGF BE regulates interstitial collagenase in Ob cells by transcr iptional and posttranscriptional mechanisms, and this effect may contr ibute to its stimulatory actions on bone collagen degradation.