title: Systemic administration of an anabolic dose of PGE2 in young rats increases the osteogenic capacity of bone marrow.
abstract: Prostaglandin E2 (PGE2) possesses significant anabolic properties when 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 PGE2 into young rats and showed it increases cortical and cancellous bone mass and mechanical strength in long bones and bone density in the calvaria. We also found that a single dose of PGE2 induces the expression of early-response genes (c-fos, c-jun, and egr-1) in bone marrow cells within these two types of bone. These observations, together with findings by others of new cancellous bone formation in PGE2-treated animals, suggested that recruitment of osteoblasts from their precursors is a major mechanism of the anabolic effect of PGE2. To test this hypothesis directly, we injected PGE2 (6 mg/kg) or vehicle into 4-week-old rats for 2 weeks and then assessed the osteogenic potential of bone marrow in an ex vivo culture system. Primary and first-passage bone marrow cultures were established in the presence of beta-glycerophosphate, ascorbate, and dexamethasone, and osteogenic differentiation was measured by bone nodule formation and alkaline phosphatase activity. This regimen increased bone mass 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 primary and first-passage cultures from PGE2-treated rats despite seeding of the same number of marrow cells. Alkaline phosphatase activity was elevated in both primary and first-passage cultures from PGE2-treated rats beginning 6-10 days after culture initiation. Cell proliferation was only slightly elevated in cultures from PGE2-treated rats. These data strongly suggest that in vivo administration of PGE2 induces the proliferation or differentiation of osteoprogenitor cells in bone marrow, and this effect takes a major part in its anabolic effect in vivo.
authors.affiliation: Department of Oral Biology, Maurice and Gabriela Goldschleger School of Dental Medicine, Tel-Aviv University, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Weinreb
authors.forename: I
authors.initials: I
authors.lastname: Suponitzky
authors.forename: S
authors.initials: S
authors.lastname: Keila
mesh_terms: D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D001842:Bone and Bones / Q000187:drug effects; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D010120:Oxytocics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010120:Oxytocics; D000469:Alkaline Phosphatase; D015232:Dinoprostone