Actions of bFGF on mitogenic activity and lineage expression in rat osteoprogenitor cells: effect of age

Rat osteoprogenitor cells were used to examine the effects of bFGF on DNA s ynthesis and the expression of osteoblast (OB)-related genes, bFGF, as low as 0.1 ng/ml, stimulated DNA synthesis. bFGF also increased the mRNA level of osteopontin (OP) and decreased that of type I collagen (COL I). When cul tures were grown in dexamethasone (DEX) to induce OB lineage commitment, th e expression of COL I, alkaline phosphatase (AP) and OP was greatly enhance d. Subsequent incubation with bFGF partially negated the stimulatory effect of DEX on AP and COL I mRNAs. bFGF also inhibited the expression of osteoc alcin mRNA in cells grown in 1,25(OH)(2)D-3 and DEX. Combined effects of bF GF with IGF-I or PDGF on DNA synthesis and OP expression were examined. bFG F + IGF-I, but not bFGF + PDGF, was more effective than PDGF alone. By comp aring cells from adult and old animals, we found that bFGF-induced mitogeni c activity was reduced significantly with age. In contrast, the effect of b FGF on the expression of OB genes was not significantly altered by age. The se findings suggest that bFGF plays a dual role as a local positive and neg ative regulator on proliferation and osteogenic lineage expression, respect ively, in osteoprogenitor cells, and that the mitogenic activity in respons e to bFGF was impaired in aging. (C) 1999 Published by Elsevier Science Ire land Ltd. All rights reserved.