Differential sensitivity of osteoclasts and osteoblasts suggests that prostaglandin E 1 effects on bone may be mediated primarily through the osteoclasts

Abstract

Prostaglandin E (PGE) stimulates resorption in bone. Since osteoblast-like osteosarcoma cells secrete PGE 2, 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, PGE 1 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 PGE 1 can activate OC cells at doses as low as 1 n m, whereas OB cells require 250 n m. Bone cell responses to various doses of PTH and PGE 1 were also compared. In OC cells the lowest effective dose of PGE 1 and PTH was similar (1 n m), but increasing response to PGE 1 was seen up to 1000 n m in contrast to PTH response which peaked at 20 n m. In addition, the magnitude of PGE 1-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 n m, compared to 250 n m for PGE 1. Half-maximal inhibition of citrate decarboxylation (19% of control) by PTH occurred at 0.5 n m, whereas 500 n m of PGE 1 was required for an equivalent effect. Thus, ( i) OC cells responded to PGE 1 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 PGE 1.