S. Varghese et al., TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL REGULATION OF INTERSTITIAL COLLAGENASE BY PLATELET-DERIVED GROWTH-FACTOR BB IN BONE CELL-CULTURES, Endocrinology, 137(2), 1996, pp. 431-437
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.