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 in cultures of osteoblast-enriched cells from fetal rat calvariae (Ob cells). After 4-8 h of treatment, PDGF BB at 0.3 nM increased steady state collagenase messenger RNA (mRNA), whereas PDGF AA had no effect. The effect of PDGF BB on collagenase transcripts was dose dependent. PDGF BB increased the levels of immunoreactive collagenase after 6 h, whereas the levels were decreased after 16 h. Stimulation of collagenase mRNA by PDGF BB was dependent on de novo protein synthesis and activation of protein kinase C. PDGF BB prolonged the half-life of collagenase mRNA in transcriptionally arrested cells. PDGF BB initially increased and subsequently decreased the rate of collagenase gene transcription and the levels of collagenase heterogeneous nuclear RNA. In conclusion, PDGF BB regulates interstitial collagenase in Ob cells by transcriptional and posttranscriptional mechanisms, and this effect may contribute to its stimulatory actions on bone collagen degradation.
Varghese
S
S
Department of Research and Medicine, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA.
Delany
A M
AM
Liang
L
L
Gabbitas
B
B
Jeffrey
J J
JJ
Canalis
E
E
D000818:Animals; D001483:Base Sequence; D000077214:Becaplermin; D001842:Bone and Bones / Q000166:cytology / Q000201:enzymology*; D002478:Cells, Cultured; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D005110:Extracellular Space / Q000201:enzymology*; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D014158:Transcription, Genetic
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000077214:Becaplermin; D017364:Collagenases