Cyclooxygenases and prostaglandin E2 receptors in growth plate chondrocytes in vitro and in situ – prostaglandin E2 dependent proliferation of growth plate chondrocytes

摘要: Prostaglandin E2 (PGE2) plays an important role in bone development and metabolism. To interfere therapeutically the PGE2 pathway, however, knowledge about involved enzymes (cyclooxygenases) receptors (PGE2 receptors) is essential. We therefore examined production of cultured growth plate chondrocytes vitro effects exogenously added on cell proliferation. Furthermore, we analysed expression spatial distribution cyclooxygenase (COX)-1 COX-2 receptor types EP1, EP2, EP3 EP4 situ vitro. synthesis was determined by mass spectrometry, proliferation DNA [3H]-thymidine incorporation, mRNA cyclooxygenases EP RT-PCR cells homogenized plates. determine cellular expression, frozen sections rat tibial primary chondrocyte cultures were stained using immunohistochemistry with polyclonal antibodies directed towards COX-1, COX-2, EP3, EP4. Cultured transiently secreted into culture medium. Although both expressed vivo, it appears that mainly contributed to PGE2-dependent Exogenously stimulated a dose-dependent fashion gave bell-shaped curve maximum at 10-8 M. The EP1/EP3 specific agonist sulprostone EP1-selective ONO-D1-004 increased synthesis. effect suppressed ONO-8711. observed; EP2 homogenously all zones situ, whereas EP1 inhomogenous, spared reserve zone. In these four subset only. most intense staining for found polygonal surrounded matrix. Expression protein observed also chrondrocytes, only weak detected. suggest chondrocytes, responsible release, which stimulates via receptor.