Differential actions of prostaglandins in separate cell populations from fetal rat bone

Prostaglandins (PGs) may stimulate or inhibit bone cell replication and protein synthesis. These disparities may be concentration or time dependent, or occur in discrete cell types or by different second signals. Cell populations that express progressive degrees of osteoblast-like activity can be obtained by serial collagenase digestion of fetal rat parietal bone. The first (population 1) appears less differentiated, whereas the later (populations 3-5) exhibit biochemical features characteristic of osteoblasts. Within 24 h of treatment, three separate PGs increased DNA synthesis in population 1 with relative potencies of PGE1 < PGE2 < PGF2 alpha. By contrast, PGE1 and PGE2 (both strong cAMP inducers) inhibited basal DNA synthesis in population 3-5. These differences were paralleled by analogous changes in collagen and noncollagen synthesis in each population. The mitogenic effect in population 1 persisted for 72 h, and at later times was sensitive to indomethacin. These changes were unlikely to be cAMP dependent, as PGF2 alpha did not induce cAMP production, and the cAMP inducer forskolin was inhibitory. Moreover, phorbol ester treatment enhanced DNA synthesis to a greater extent in population 1 than in populations 3-5, and cotreatment with H-8 (at Km, approximately 10 microM) and staurosporine (at Km, approximately 0.01 microM) decreased the mitogenic effect of PGs in population 1, consistent with a reduction in protein kinase-C activation. These studies suggest that PGs activate less differentiated bone cells by a protein kinase-dependent event, whereas cAMP (induced by PGE1 and PGE2) decreases DNA and protein synthesis in more differentiated bone cells and tempers the increase in cellular activation found in population 1. Consequently, agents or events that increase the synthesis of specific PGs could differentially regulate, in positive and negative ways, biochemical activities in discrete bone cell populations.