The effect of parathyroid hormone, 1,25-dihydroxycholecalciferol and prostaglandins on the cytoplasmic activity of isolated osteoclasts.

Abstract

AbstractOsteoclasts were isolated on glass or plastic substrates and the effect of bone‐active hormones and prostaglandins on their behaviour was observed. Untreated osteoclasts migrate across the substratum, actively extending pseudopodia which show intense “rippling” activity. Addition of parathyroid hormone (PTH), 1,25‐dihydroxycholecalciferol (1,25‐(OH)2D3), prostaglandins (PG) F2α, E2 and thromboxane B2 caused no change in the behaviour or morphology of these osteoclasts. Prostacyclin, however, caused rapid cessation of cytoplasmic rippling activity followed by gradual pseudopodial retraction in a manner indistinguishable from that previously observed in the presence of calcitonin. The cytoplasmic quiescence induced by prostacyclin was seen at concentrations of 10−9M and above. Quiescence was reversible and its duration depended upon the dose of the compound administered (prostacyclin decays rapidly). No such effect was observed on the behaviour of the other cell types contaminating the osteoclast cultures, nor on purified populations of osteoblasts or peritoneal macrophages.We also tested the ability of PTH, 1,25‐(OH)2D3 and PGs to reverse calcitonin‐induced osteoclast quiescence. We found that even high doses showed no detectable stimulation of quiescent isolated osteoclasts. This suggests that the undoubted ability of these hormones to stimulate osteoclastic activity in vivo is mediated indirectly, following a primary hormonal interaction with another cell type.We propose a model for the control of osteoclasis based on these observations. Prostacyclin may play the role of a local‐acting hormone, produced by osteoblasts, which terminates osteoclasis when the requirements of local bone morphogenesis are fulfilled. Calcitonin exerts a direct inhibitory action on isolated osteoclasts and we suggest that this is opposed in vivo by an osteoclastic stimulator, released by osteoblasts. The hormones PTH, 1.25‐(OH)2,D3, and PGE2, stimulate osteoclastic activity indirectly following a primary interaction with osteoblasts, and may do so either by reducing the release of prostacyclin by osteoblasts or increasing formation of the unknown stimulator, or both.