S. Rydziel et al., TRANSFORMING GROWTH-FACTOR-BETA-1 INHIBITS COLLAGENASE-3 EXPRESSION BY TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL MECHANISMS IN OSTEOBLAST CULTURES, Journal of cellular physiology, 170(2), 1997, pp. 145-152
Transforming growth factor (TGF) beta 1 is an autocrine regulator of b
one cell function. We demonstrated that TGF beta 1 enhances bone colla
gen synthesis, but its effects on collagen degradation are not well ch
aracterized We tested the effects of TGF beta 1 on rat collagenase 3 e
xpression in cultures of osteoblast-enriched cells from fetal rat calv
ariae (Ob cells). Treatment with TGF beta 1 at 0.4 nM decreased steady
state collagenase mRNA levels after 2 to 24 h. This dose-dependent ef
fect was observed at TGF beta 1 concentrations of 4 pM to 1.2 nM, and
was accompanied by decreased levels of immunoreactive procollagenase.
The protein synthesis inhibitor cycloheximide increased collagenase tr
anscripts, but did not prevent the effect of TGF beta 1 on collagenase
mRNA levels. TGF beta 1 accelerated the decay of collagenase mRNA in
transcriptionally arrested Ob cells. In addition, TGF beta 1 decreased
the levels of collagenase heterogeneous nuclear RNA and the rate of c
ollagenase gene transcription in Ob cells. TGF beta 1 enhanced the exp
ression of tissue inhibitors of metalloproteinases (TIMP) 1 and 3 and
caused a modest decrease of TIMP 2 mRNA levels. in conclusion, TGF pi
decreases interstitial collagenase transcripts and protease levels in
Ob cells by transcriptional and post-transcriptional mechanisms, and t
his effect may contribute to its actions on bone matrix. (C) 1997 Wile
y-Liss, inc.