Estrogen enhances progesterone-induced stimulation of proliferation and differentiation of osteoprogenitors in cell populations derived from adult human bone

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Previous experiments have demonstrated that bone cell populations derived from explants of lumbar vertebral bone of adult female rats contain osteoprogenitors that require dexamethasone (Dex) or progesterone (Prog) to proliferate and differentiate into fully differentiated bone-forming osteoblasts. This study was conducted to determine whether these findings found in rat are also observed in human using human cells. First, the present study was undertaken to determine the frequency and/or number of Dex and Prog-responsive osteoprogenitors in cell populations. Frequencies and numbers of progenitor types were determined for up to six subcultures using continuous subculturing, limiting dilution analysis, and colony assays. In Dex-containing medium, subculturing resulted in a 10% increase in the total number of Dex-responsive osteoprogenitors in second subculture cells over first subculture cell. From the third subculture onward, the frequency of osteoprogenitors decreased in a linear mann … More er and none were observed after five subcultures. Similar results were obtained in Prog-containing medium. Limiting dilution analysis in the presence of Dex indicated that 1.81% of cells represented a colony forming unit-fibroblast and 0.25% represented an osteoprogenitor in first subculture cells. In the presence of Prog indicated that 1.75% of cells represented a colony forming unit-fibroblast and 0.09% represented an osteoprogenitor in first subculture cells. Second, we show that the Prog-dependent population can be detected in female bone after sexual maturation, and can be induced by culturing the osteoprogenitors in media containing 17 β-estradiol (10-9-10-8m). This suggested that the survival of the Prog-dependent osteoprogenitors and/or their ability to proliferate is dependent on the presence of estrogen. The results presented here are compatible with the view that in the female skeleton one of the mechanisms maintaining bone mass is related to effects of both estrogen and Prog on a class of osteoprogenitors responsive to Prog. These findings may provide new insight into the significance of a specific class of Prog-dependent osteoprogenitors and of their regulation by estrogen in the human skeleton. Less