SYSTEMIC ADMINISTRATION OF AN ANABOLIC DOSE OF PGE(2) IN YOUNG-RATS INCREASES THE OSTEOGENIC CAPACITY OF BONE-MARROW

Prostaglandin E-2 (PGE(2)) possesses significant anabolic properties w hen administered systemically (i.e., it increases bone formation and, consequently, bone mass), We recently characterized the effects of a 3 week administration of 6 mg/kg PGE(2) into young rats and showed it i ncreases cortical and cancellous bone mass and mechanical strength in long bones and bone density in the calvaria, We also found that a sing le dose of PGE(2) induces the expression of early-response genes (c-fo s, c-jun, and egr-1) in bone marrow cells within these two types of bo ne, These observations, together with findings by others of new cancel lous bone formation in PGE(2)-treated animals, suggested that recruitm ent of osteoblasts from their precursors is a major mechanism of the a nabolic effect of PGE(2). To test this hypothesis directly, we injecte d PGE(2) (6 mg/kg) or vehicle into 4-week-old rats for 2 weeks and the n assessed the osteogenic potential of bone marrow in an ex vivo cultu re system, Primary and first-passage bone marrow cultures were establi shed in the presence of beta-glycerophosphate, ascorbate, and dexameth asone, and osteogenic differentiation was measured by bone nodule form ation and alkaline phosphatase activity, This regimen increased bone m ass expressed as femoral ash weight by 4.7% and tibial cancellous bone area by 38.3%, Nodule formation at 21 days was increased in both prim ary and first-passage cultures from PGE(2)-treated rats despite seedin g of the same number of marrow cells, Alkaline phosphatase activity wa s elevated in both primary and first-passage cultures from PGE(2)-trea ted rats beginning 6-10 days after culture initiation, Cell proliferat ion was only slightly elevated in cultures from PGE(2) treated rats, T hese data strongly suggest that in vivo administration of PGE(2) induc es the proliferation or differentiation of osteoprogenitor cells in bo ne marrow, and this effect takes a major part in its anabolic effect i n vivo. (C) 1997 by Elsevier Science Inc.