The effects of prostaglandin E2 in growing rats: Increased metaphyseal hard tissue and cortico-endosteal bone formation

Abstract

To assess the efficacy of PGE2 in inducing in vivo bone formation, graded doses of prostaglandins E2 were administered to 255 g rats. Histomorphometric analyses of selected sequential fluorescent-labeled bones of rats treated with 0, 0.3, 1.0, 3, or 6 mg PGE2/kg/d for 21 days showed that the doses PGE2 depressed longitudinal bone growth, increased growth cartilage thickness slightly, decreased degenerative cartilage cell size and cartilage cell production slightly, and increased proximal tibial metaphyseal hard-tissue mass markedly. Periosteal bone formation was depressed at the higher doses, and an early, slight depression in endosteal bone formation was also observed, along with a striking late increase in endosteal bone formation and in the formation of trabecular bone in the marrow cavity of the tibial shaft. The characteristics and magnitude of these responses were quite similar to those observed in our previous study of the effects of PGE2 on weanling rats except for the delayed increase in cortico-endosteal bone formation.

Neurogenic heterotopic ossification in spinal cord injury

“…In animal studies it has been suggested that eg prostaglandin E2 (PGE2) and interleukin-1 can induce a dose dependent increase in the subperiostal lamellar bone formation 90 and that subcutaneous injections of PGE2 in growing rats can induce heterotopic bone formation. 91,92 Measurement of 24-h PGE in SCI patients with NHO showed abnormal 24-h PGE2 urinary excretion as long as the bone-scan had not stabilized. 27 However, the mechanism by which prostaglandins may induce ectopic bone formation in SCI patients remains unclear and there are well-known di culties in the interpretation of PGE2 urinary excretion measurements in men presenting with a positive urinary sperm count or in patients with lower urinary tract infections.…”

Prostaglandin Promotion of Osteocyte Gap Junction Function through Transcriptional Regulation of Connexin 43 by Glycogen Synthase Kinase 3/β-Catenin Signaling

“…An osteocyte-like cell line, MLO-Y4, has been shown to have characteristics of primary osteocytes (27). We and others have shown that MLO-Y4 cells are functionally coupled by gap junction channels and that Cx43 is a major gap junction protein expressed in primary osteocytes and MLO-Y4 cells (8,23,27,36,45,47). Mechanical forces applied to bone cause fluid to flow through the canaliculi surrounding the osteocyte, and that fluid flow shear stress releases prostaglandins and other bone modulators (40) required for bone modeling and remodeling.…”

Effects of Mechanical Strain on the Function of Gap Junctions in Osteocytes Are Mediated through the Prostaglandin EP2 Receptor

“…Prostaglandins are generally thought to be skeletal anabolic agents, because administration of these agents can increase bone mass in various animal species (25)(26)(27), stimulate bone formation in vitro in organ culture (28), and increase nodule formation in rat calvarial osteoblasts (29,30). Prostaglandins also have catabolic effects on bone and have been shown to stimulate osteoclastic bone resorption and osteoclast formation and activation (28,(31)(32)(33)(34).…”