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

Abstract

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