Systemic prostaglandin E-2 increases cancellous bone formation and mass inaging rats and stimulates their bone marrow osteogenic capacity in vivo and in vitro

Prostaglandin E-2 (PGE(2)) has been shown to exert a bone anabolic effect i n young and adult rats. In this study we tested whether it possesses a simi lar effect on bone formation and bone mass in aging rats. Fifteen-month-old rats were injected daily with either PGE(2) at 5 mg/kg or vehicle for 14 d ays. PGE(2) treatment stimulated the rate of cancellous bone formation (a s imilar to5.5-fold increase in bone formation rate), measured by the incorpo ration of calcein into bone-forming surfaces at the tibial proximal metaphy sis. This effect resulted in increased cancellous bone area (+54%) at the s ame site. Since PGE(2) treatment resulted in a much higher proportion of bo ne surface undergoing bone formation and thus lined with osteoblasts, we te sted the hypothesis that PGE(2) stimulates osteoblast differentiation from bone marrow precursor cells both in vivo and in vitro. We found that ex viv o cultures of bone marrow stromal cells from rats injected for 2 weeks with PGE(2) at 5 mg/kg per day yielded more (similar to4-fold) mineralized nodu les and exhibited a greater (by 30-40%) alkaline phosphatase activity compa red with cultures from vehicle-injected rats, attesting to a stimulation of osteoblastic differentiation by PGE(2). We also compared the osteogenic capacity of bone marrow from aging (15-mont h-old) versus young (5-week-old) rats and its regulation by PGE(2) in vitro . Bone marrow stromal cell cultures from aging rats exhibited a greatly dim inished osteogenic capacity, reflected in reduced nodule formation (similar to6% of young animals) and lower alkaline phosphatase activity (similar to 60% of young animals). However, these parameters could be stimulated in bo th groups of animals by incubation with 10-100 nM PGE(2). The magnitude of this stimulation was greater in cultures from aging rats (+550% vs +70% in nodule formation of aging compared with young rats). In conclusion, we demonstrate here that PGE(2) exerts a bone anabolic effec t in aging rats, similar to the effect we and others have reported in young , growing rats. The PGE(2)-stimulated bone formation, which augments bone m ass, most likely results from recruitment of osteoblasts from their bone ma rrow stromal precursors.