DNA synthesis is not necessary for osteoclastic responses to parathyroid hormone in cultured fetal rat long bones.
Osteoclasts, the principal cells mediating bone resorption, are believed to increase their size, number, and resorbing activity in response to parathyroid hormone (PTH) through mechanisms dependent upon the fusion of specific mononuclear precursor cells into either new or existing multinucleated osteoclasts. To address the question of whether these actions of PTH are dependent on the replication of osteoclast precursor cells, we examined the ability of an inhibitor of DNA synthesis, hydroxyurea (HU), to alter bone resorption, osteoclast formation, and DNA synthesis in cultured fetal rat bones treated with PTH. We found that HU significantly reduced [3H]thymidine incorporation into the bones and labeling of osteoclast nuclei by greater than 90%, but did not prevent PTH from stimulating bone resorption, measured as the release of 45Ca, or from increasing the number of osteoclasts in the bones. In bones cultured without PTH, HU decreased the rate of bone resorption, but not the number of osteoclasts per bone. We conclude that in fetal rat bone cultures, PTH can increase osteoclast number and stimulate bone resorption by affecting existing osteoclasts and osteoclast precursors, and that replication of osteoclast precursor cells is not necessary for PTH to stimulate a resorptive response. In unstimulated cultures it appears that HU inhibits bone resorption by affecting mechanisms that are independent of changes in osteoclast number and that may be influenced by cell replication or other unknown factors.
D000818:Animals; D001862:Bone Resorption; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D005333:Fetus; D006918:Hydroxyurea / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000502:physiology*; D051381:Rats
D010281:Parathyroid Hormone; D004247:DNA; D002118:Calcium; D006918:Hydroxyurea