Age-associated changes in the stimulatory effect of transforming growth factor beta on human osteogenic colony formation.

Previous studies have indicated that the mitogenic responsiveness of human bone cells may change with age. In the present study, we examined whether aging affects the capacity of transforming growth factor beta (TGF-beta) to stimulate the colony formation of human osteoprogenitor cells. Outgrowths of bone cells from 98 iliac crest biopsies were plated at a density of 25 cells/cm2 and cultured for 3 weeks in the presence of 10% fetal calf serum. Approximately 5% of the plated cells gave rise to clonal colonies. TGF-beta (10(-11) M) significantly increased the estimated number of cells per colony. However, the stimulatory effect of TGF-beta significantly declined with donor age (r = -0.26, P = 0.01). Whereas TGF-beta raised the average number of cells per colony in cultures from donors below the age of 50 years by 136+/-50%, the average increase was only 43+/-16% in donors older than 60 years. These data raise the possibility that aging may be associated with a declining capacity of TGF-beta to enlarge the pool of bone cells that can be generated from a single human osteoblast progenitor cell.