Effect of maturation on the osteogenic response of cultured stromal bone marrow cells to basic fibroblast growth factor

Formation of bone-like tissue in culture by stromal bone marrow cells (SBMC ) derived from young growing rats is dependent on dexamethasone (Dex) (Cell Tissue Res 254:317; 1988) and is significantly enhanced by basic fibroblas t growth factor (bFGF) (J Bone Miner Res 8:919; 1993), The aim of this stud y was to examine the effect of maturation on the osteogenic potential and t he response to Dex and bFGF of SBMC by using cultures derived from young gr owing (6 weeks old) and adult (9 months old) rats. SBMC cultures were grown in the presence of Dex (10(-8) or 10(-7) mol/L) at both P-0 and P-1 and ei ther in the presence or absence of bFGF, The effect of Dex and bFGF on mine ralized bone-like tissue (MBT) formation was assessed at P-1. The highest l evels of mineralized tissue formation in P-1 subcultures in the absence of bFGF were obtained when cultures derived from young rats (6 weeks old) were treated with Dex 10(-7) and 10(-8) mol/L at P-0 and P-1, respectively, and when cultures derived from adult rats were exposed to Dex 10(-8) mol/L bot h at P-0 and P-1. Under these optimal Dex concentrations, the amount of MBT formed by adult rat-derived cultures was 15-fold lower than that of young rat-derived ones. The addition of bFGF to P-0 cultures or to P-1 cultures g rown under optimal Dex conditions enhanced MBT formation in P-1 cultures de rived from both young and adult rats, but this effect was considerably more pronounced in the adult rat-derived cultures. The maximal levels of MBT fo rmation were produced by cultures derived from adult rats treated with bFGF at both P-0 and P-1, whereas in cultures derived from young rats, the addi tion of bFGF at P-0 was not necessary for maximal MBT production. This stim ulating effect of bFGF on MBT formation by adult rat-derived cultures was a ccompanied by a 2.2-, 1.8-, and 4.3-fold increase in proliferation, alkalin e phosphatase activity, and Ca2+ deposition rate, respectively. bFGF increa sed the level of glucocorticoid receptor by approximately 2.3-fold in Dex-t reated cultures derived from young animals. These results indicate that mat uration is associated with a decrease in the proportion of osteoprogenitor cells in the stromal bone marrow and in their capacity to express the osteo genic phenotype, They further point to the significant role of bFGF in stim ulating proliferation and osteogenic expression of stromal bone marrow oste oprogenitors derived from adult rats. (C) 2000 by Elsevier Science Inc. All rights reserved.