Enhancement of parathyroid hormone-stimulated bone resorption by poly-L-lysine

Poly-L-lysine (PL II; mol wt, 1000-4000) was added to fetal rat bones cultured in a chemically defined medium (BGJ) containing bovine serum albumin in the presence and absence of parathyroid hormone (PTH). Bone resorption was measured by the release of previously incorporated 45Ca. The addition of PL II at concentrations of 3-100 microgram/ml enhanced the stimulation of bone resorption by submaximal doses of PTH but had little effect on 45Ca release from control unstimulated cultures. Higher concentrations of PL II produced inhibition of 45Ca release. Dialysis of PL II did not alter enhancement or inhibition by PL II. PL II did not increase sensitivity to PTH in serum-supplemented cultures. Higher molecular weight PL II preparations were less effective. PL II did not enhance the resorptive response to 1,25-dihydroxyvitamin D, prostaglandin E2, osteoclast-activating factor, or bacterial endotoxin. The mechanism of the selective ability of PL II to enhance the response to low concentrations of PTH is unknown but may be due to the ability of this basic polypeptide to interfere with binding of PTH to sites other than the hormone receptor or to block degradation of PTH by bone.