The Interaction of Parathormone and Calcium on the Hormone-Regulated Synthesis of Hyaluronic Acid and Citrate Decarboxylation in Isolated Bone Cells

The possible involvement of calcium in the action of parathormone on bone cell metabolism in culture was evaluated. Previously, we showed that parathormone stimulated hyaluronate synthesis in osteoclast like (CT) cells and inhibited citrate decarboxylation in osteoblast-like (PT) cells in culture. In the present study, in the absence of parathormone, elevation of calcium concentration in the medium from a normal level of 1.8–5.8 mM mimicked the actions of parathormone on both biochemical activities as to maximum effect and time course. As with parathormone, the change produced by calcium on hyaluronate synthesis was confined to osteoclast-like cells and the change in citrate metabolism was confined to the osteoblast-like cells. Below 5 mM calcium, parathormone stimulated hyaluronate synthesis or inhibited citrate decarboxylation further, but never beyond that produced by the maximally effective levels of either the parathormone or calcium alone. In the absence of calcium in the medium, parathormone did not alter either hyaluronate synthesis or citrate decarboxylation but was fully capable of stimulating bone cell adenylate cyclase. Moreover, elevated calcium did not by itself change cellular levels of cAMP, thus ruling out the possibility that calcium acted through stimulation of parathormone-activated adenylate cyclase. Calcitonin, while effective in blocking parathormone stimulated hyaluronate synthesis in osteoclast like cells, did not inhibit the similar increase produced by calcium. One interpretation of these results is that parathormone acts on bone cells by altering membrane permeability and allowing calcium to enter the cell as a mediator of hormone action. The inability of calcitonin to block the action of calcium could mean that this peptide affects osteoclasts at a point at or before the site at which parathormone affects calcium influx.