Differential sensitivity of osteoclasts and osteoblasts suggests that prostaglandin E1 effects on bone may be mediated primarily through the osteoclasts.
Prostaglandin E (PGE) stimulates resorption in bone. Since osteoblast-like osteosarcoma cells secrete PGE2, the possibility that osteoclasts were the major target for PGE was considered. To study this question, it was first established that in isolated bone cells enriched for either osteoclastic (OC) or osteoblastic (OB) characteristics, PGE1 can induce biochemical effects similar to those seen with bovine parathyroid hormone 1-84 (PTH), another potent stimulator of bone resorption. These changes include increased cAMP and hyaluronate synthesis in OC cells, and increased cAMP but decreased citrate decarboxylation in OB cells. By following these markers, it is demonstrated that PGE1 can activate OC cells at doses as low as 1 nM, whereas OB cells require 250 nM. Bone cell responses to various doses of PTH and PGE1 were also compared. In OC cells the lowest effective dose of PGE1 and PTH was similar (1 nM), but increasing response to PGE1 was seen up to 1000 nM in contrast to PTH response which peaked at 20 nM. In addition, the magnitude of PGE1-induced OC cell hyaluronate was two to four times greater than that of PTH at all doses tested. In OB cells, PTH induced significant decreases in citrate decarboxylation at 0.1 nM, compared to 250 nM for PGE1. Half-maximal inhibition of citrate decarboxylation (19% of control) by PTH occurred at 0.5 nM, whereas 500 nM of PGE1 was required for an equivalent effect. Thus, (i) OC cells responded to PGE1 doses that were approximately 200 times lower than the minimum required by OB cells, and (ii) OB cells responded to 100 times lower doses of PTH than PGE1.
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*
D010281:Parathyroid Hormone; D011458:Prostaglandins E; D000242:Cyclic AMP