Prostaglandin E2 (PGE2) autoamplifies its production through EP1 subtype of PGE receptor in mouse osteoblastic MC3T3-E1 cells

Prostaglandin E-2 (PGE(2)) is known to autoamplify its production in the osteoblasts through the induction of prostaglandin G/H synthase-2 (PGHS-2), which is the inducible form of the rate-limiting enzyme in PG synthesis, PGHS. To elucidate the cellular mechanism mediating this process, we have employed the PGE(2) analogs, which are specific agonists for four subtypes of PGE receptor, and studied the potency of these analogs to induce PGHS-2 mRNA in mouse osteoblastic MC3T3-E1 cells. The induction was mainly observed by 17-phenyl-omega-trinor PGE(2) (EP1 agonist) and sulprostone (EP3/EP1 agonist), but not by butaprost (EP2 agonist) or 11-deoxy PGE(1) (EP4/EP2 agonist). Since EP3 subtype was undetectable in MC3T3-E1 cells, these data indicate that PGHS-2 mRNA induction is mediated through EP1 subtype of PGE receptor in MC3T3-E1 cells. PGE(2) production determined by radioimmunoassay was also increased by 17-phenyl-omega-trinor PGE(2) and sulprostone. The autoamplification of PGE(2) production is considered to be important in elongating the otherwise short-lived PGE(2) action in certain physiological conditions such as mechanical stress and fracture healing, as well as the pathological inflammatory bone loss. The observations in the present study provide us with the better understanding of these processes.