Faculty Bibliography

The effects of phenytoin (diphenylhydantoin, DPH) on calcium uptake in osteoblastic cells were studied to elucidate the potential mechanism of action of this antiepileptic drug on bone metabolism. Preincubation of the human osteoblastic osteosarcomal cell line, SaOS-2, and normal rat osteoblastic cells with DPH decreased basal calcium uptake. This inhibition occurred at DPH doses from 0.1 to 50 micrograms/ml. Parathyroid hormone (PTH) and prostaglandin E2 (PGE2) increased calcium uptake in the SaOS-2 cell line. Following preincubation with DPH, calcium uptake in cells treated with PTH or PGE2 did not exceed control levels. However, significant increases in the PTH- or PGE2-treated + DPH-pretreated cells compared to DPH pretreatment alone were still observed. These studies indicate that DPH induces decreases in osteoblastic calcium influx and they add further information on the possible mode of action of this drug on bone.

Calcitonin causes an increase in the accumulation of cAMP in mammalian osteoclasts leading to an inhibition of bone resorption. Increases in cAMP subsequent to calcitonin stimulation have not been detected in previous studies of chicken osteoclasts as the only source of large numbers of highly purified cells. In this report, we studied the effects of salmon calcitonin (sCT), bovine parathyroid hormone -(1-34) [(bPTH -(1-34)] and forskolin (FSK) on cAMP accumulation in freshly isolated osteoclasts obtained non-enzymatically from the metaphysis of 5-7 week old rachitogenic chickens. Parathyroid hormone did not stimulate the accumulation of intracellular cAMP. Calcitonin and forskolin treatment caused a nearly 2.5 and 3.5-fold increase in cAMP respectively. This study demonstrates that chicken osteoclasts respond to calcitonin with an increase in cAMP accumulation and that the rachitogenic chicken may be a valuable source of hormonally sensitive cells for the study of osteoclast biology