Hormonal Control of Bone Collagen Synthesisin Vitro: Effects of Parathyroid Hormone and Calcitonin

Abstract

The effects of parathyroid hormone (PTH) on bone collagen synthesis were assessed in organ cultures of fetal rat calvaria by measuring the incorporation of [3H]proline into collagenase-digestible (CDP) and non-collagen protein (NCP) using purified bacterial collagenase. 1) PTH decreased the incorporation of labeled proline into CDP at concentrations similar to those which stimulate bone resorption in vitro. 2) This effect was observed in bones treated for 6 h, but not for 3 h; it was maximal at 24 h and was maintained for 96 h. Bones treated with PTH for 48 h and transferred to control media for 48 h showed recovery of CDP labeling to control values. 3) the effect was specific for bone collagen. There was little alteration in the incorporation of proline into NCP, and incorporation into collagen was not inhibited. 4) The effect could be ascribed to decreased collagen synthesis and not to changes in amino acid uptake, precursor pool size, or degradation of newly synthesized CDP. In 3 hour experiments, PTH did increase the labeling of CDP and NCP, but only at tracer concentration of proline in the medium, compatible with an early stimulation of amino acid uptake. 5) Similar inhibition was observed with purified bovine (1-84) PTH and synthetic bovine PTH (1-34) as well as with crude homologous PTH obtained from rat parathyroid gland culture fluid. Human (hCT) and salmon (sCT) calcitonin did not inhibit the effect of PTH on the labeling of CDP nor did they stimulate CDP labeling directly at concentrations which inhibited bone resorption. Dibutyryl cyclic-3',5'-adenosine monophosphate (D3cAMP) inhibited labeling of CDP at concentrations of .03 to .3 mM, thus mimicking the action of PTH. However, in this system DBcAMP inhibited 45Ca release, thus mimicking CT. We conclude that the direct effect of PTH on bone collagen synthesis is a slow reversible inhibition, not opposed by CT. This effect may be mediated by cAMP formation in bone cells.

Glucocorticoid Receptors and Actions in Subpopulations of Cultured Rat Bone Cells

“…The second action is a potentiation of PTH-stimulated cAN1P production. PTH inhibits OB cell activity and decreases collagen formation (25,26). cAMP is considered the intracellular mediator of these effects (26).…”

“…PTH inhibits OB cell activity and decreases collagen formation (25,26). cAMP is considered the intracellular mediator of these effects (26). Therefore, by potentiating PTH action, glucocorticoids maxv inhibit OB cells by a second pathway.…”

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

“…Since PTH is a negative regulator of collagen synthesis, this could then lead to altered type I collagen production in OA bone tissue [83,84].…”

Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures.

“…PTH stimulates bone cell replication in vitro, but continuous exposure to PTH results in decreased collagen synthesis in cultured calvariae (4,5). In contrast, in vivo studies have shown that PTH increases bone formation (6,7).…”