Effects of parathyroid hormone and calcitonin on osteoclast formation in vitro.
We have investigated hormonal interactions regulating bone resorption by measuring biochemical and morphological responses of neonatal mouse calvaria in vitro to treatment with 0.1 U/ml parathyroid hormone (PTH) without or with 100 ng/ml human calcitonin (CT). Calvaria were also labeled continuously with 0.5 microCi [3H]thymidine/bone. By 96 h, PTH stimulated the release of calcium (Ca) into the medium to 240% of control, while CT alone stimulated release of Ca to 96% of control. CT in the presence of PTH transiently inhibited the release of Ca up to 24--48 h after its addition. The subsequent loss of responsiveness to CT has been described as escape. Light microscopic analysis showed that PTH treatment markedly increased the number of osteoclast profiles in parallel with the stimulation of Ca release. Ct in the presence of PTH only transiently slowed the increase in osteoclast profiles. Fewer osteoclast profiles were observed in the presence of CT alone than in the control. Autoradiography of PTH-treated bones first showed [3H]thymidine label in osteoclast nuclei at 24 h, which increased markedly by 96 h. In PTH- plus CT-treated calvaria, significantly fewer osteoclast nuclei were labeled even at 96 h. In summary, hormonally induced changes in osteoclast profiles correlated well with changes in the stimulated release of Ca from calvaria. PTH had at least two effects on cell kinetics: 1) an early effect to increase the number of osteoclasts by fusion of preexisting mononuclear osteoclast precursors, and 2) a later effect to increase the fusion of postmitotic mononuclear cells with osteoclasts. In parallel with the observation of escape, CT only transiently inhibited PTH-stimulated osteoclast formation. The transient inhibition by CT of PTH-stimulated resorption can be explained by an early effect on osteoclast precursor cell fusions.
D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001692:Biological Transport / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology*; D002116:Calcitonin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D009924:Organ Culture Techniques; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D010281:Parathyroid Hormone; D002116:Calcitonin; D002118:Calcium; D013936:Thymidine