12013525

pubmed:Citation

3-4

Prostaglandin E2 (PGE2) can stimulate bone resorption by a cyclic AMP-dependent pathway. Two PGE2 receptors, EP2 and EP4 have been shown to play a role in PGE2 stimulation of osteoclast formation. In primary osteoblastic cell cultures from EP2 wild type (EP2 +/+) mice, PGE2 (0.1 microM) increased cyclic AMP production 3.5-fold, but PGE2 had no effect on cells from mice in which the EP2 receptor had been deleted (EP2 -/-). To examine the role of the EP2 receptor in the resorption response in vivo we injected PGE2 in EP2 -/- mice, and compared them with EP2 +/+ mice. Injection of PGE2 (3 mg/kg, four times daily for three days) in 9- to 12-month-old male mice on a 129 SvEv background increased serum calcium from 9.8 +/- 0.5 to 10.7 +/- 0.3 mg/dl (P < 0.01) in EP2 +/+ mice but not in EP2 -/- mice (10.1 +/- 0.3 vs. 10.2 +/- 0.3 mg/dl). PGE2 injection (6 mg/kg twice a day for three days) in 3-4 month old male mice on a C57 BL/6 X 129 SvEv background increased calcium from 8.2 +/- 0.1 to 9.0 +/- 0.3 mg/dl (P < 0.05) in EP2 +/+ mice but had no effect in EP2-/- mice (8.4 +/- 0.1 vs. 8.3 +/- 0.2 mg/dl). Injection of PGE2 over the calvariae of EP2 +/+ and EP2-/- mice increased the expression of receptor activator of nuclear factor kappaB ligand (RANKL) both locally and in the tibia, but RANKL responses were lower in EP2 -/- mice. We conclude that EP2 receptor plays a role in the hypercalcemic response to PGE2. This impaired response in EP2 -/- mice may be due to decreased ability to stimulate cyclic AMP and in part, to a smaller increase in the expression of RANKL mRNA.

eng

IM

MEDLINE

1098-8823

Print

NLM

173-80

pubmed-meshheading:12013525-Actins, pubmed-meshheading:12013525-Adenylate Cyclase, pubmed-meshheading:12013525-Animals, pubmed-meshheading:12013525-Blotting, Northern, pubmed-meshheading:12013525-Bone and Bones, pubmed-meshheading:12013525-Calcium, pubmed-meshheading:12013525-Carrier Proteins, pubmed-meshheading:12013525-Cyclic AMP, pubmed-meshheading:12013525-Dinoprostone, pubmed-meshheading:12013525-Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating), pubmed-meshheading:12013525-Glycoproteins, pubmed-meshheading:12013525-Hypercalcemia, pubmed-meshheading:12013525-Male, pubmed-meshheading:12013525-Membrane Glycoproteins, pubmed-meshheading:12013525-Mice, pubmed-meshheading:12013525-Mice, Inbred C57BL, pubmed-meshheading:12013525-Mice, Knockout, pubmed-meshheading:12013525-Osteoblasts, pubmed-meshheading:12013525-Osteoclasts, pubmed-meshheading:12013525-Osteogenesis, pubmed-meshheading:12013525-Osteoprotegerin, pubmed-meshheading:12013525-RANK Ligand, pubmed-meshheading:12013525-RNA, Messenger, pubmed-meshheading:12013525-Receptor Activator of Nuclear Factor-kappa B, pubmed-meshheading:12013525-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:12013525-Receptors, Prostaglandin E, pubmed-meshheading:12013525-Receptors, Prostaglandin E, EP2 Subtype, pubmed-meshheading:12013525-Receptors, Tumor Necrosis Factor

Prostaglandin receptor EP2 mediates PGE2 stimulated hypercalcemia in mice in vivo.

Journal Article, Research Support, U.S. Gov't, P.H.S.