Inhibitory effect of okadaic acid on bone resorption in neonatal mouse calvaria in vitro: Protein dephosphorylation as an important regulatory mechanism in the bone resorption process

Abstract

Okadaic acid (OA), a potent inhibitor of protein phosphatase type 1 and protein phosphatase type 2A was studied for its effect on bone resorption in neonatal mouse calvaria. OA (0.01 to 1000 ng/ml) had no effect on the basal bone resorption rate, except at 1000 ng/ml, were a small inhibitory effect was observed. Resorption stimulated by parathyroid hormone (10 −8 M) was abolished in the presence of OA, half maximal inhibition being observed at 1 ng/ml. However, at 50 ng/ml or higher, OA significantly increased lactate dehydrogenase activity in the medium, indicating a cytotoxic effect at these concentrations. Similar inhibitory effects were observed when bone resorption was stimulated by 1,25-dihydroxycholecalciferol (10 −8 M) or prostaglandin E 2 (10 −6 M). From this it is concluded that protein dephosphorylation may represent an important regulatory mechanism in the bone resorption process.