BASIC FIBROBLAST GROWTH-FACTOR STIMULATES EXPRESSION OF INTERSTITIAL COLLAGENASE AND INHIBITORS OF METALLOPROTEINASES IN RAT BONE-CELLS

Basic fibroblast growth factor (bFGF) is a bone cell mitogen that affe cts osteoblastic function by suppressing type I collagen synthesis. Th e investigators in this study examined whether bFGF also regulates int erstitial collagenase and tissue inhibitors of metalloproteinases (TIM Ps) in osteoblast-enriched cells isolated from 22-day fetal rat calvar iae. After exposure to 600 pM bFGF, interstitial collagenase messenger RNA (mRNA) levels, as determined by Northern hybridization analysis, increased after 2 h and were maximally stimulated to approximately 13- fold at 6 h. Exposure of osteoblast-enriched cells to 0.06-6 nM bFGF i ncreased collagenase mRNA in a dose-dependent manner, and bFGF also in creased immunoreactive collagenase measured in the culture medium by W estern blot analysis. The protein synthesis inhibitor cycloheximide, a s well as two inhibitors of protein kinase C, staurosporine and sangiv amycin, prevented the bFGF induction of collagenase transcripts, where as indomethacin, an inhibitor of prostaglandin synthesis, decreased th e effect of bFGF on collagenase mRNA levels by about 50%. After exposu re to 600 pM bFGF, levels of TIMP 1 and TIMP 3 mRNAs were also maximal ly stimulated to approximately 6-fold at 16 h and 4-fold at 6 h. bFGF did not modify TIMP 2 expression. In conclusion, bFGF may modulate deg radation of collagenous bone matrix by inhibiting collagen as well as stimulating collagenase and TIMPs by osteoblasts.