Effects of parathormone and calcitonin on citrate and hyaluronate metabolism in cultured bone.
Two metabolic correlates of parathormone-induced bone resorption are increased synthesis of hyaluronate and decreased production of CO2 from citrate. We have examined these phenomena simultaneously with calcium release in cultured mouse calvaria and fetal rat radii and ulnae treated with parathormone and calcitonin, separately or in combination. In both types of tissue the parathormone dose-response curves for inhibition of citrate decarboxylation, enhanced hyaluronate synthesis, and increased release of calcium were identical when measured 48 h after treatement. In each case a minimum response occurred at approximately 0.01 mug parathormone per ml and a maximum response at about 0.1 mug per ml. The time courses of these responses to parathromone were different. Hyaluronate synthesis increased within 1 h after treatment and peaked at 6 h; decarboxylation of citrate declined after 3 h; demineralization of the bone was not detected until 24 h. When parathormone-treated bones were placed in parathormone-free medium, citrate decarboxylation returned to control levels within 24 h, but increased synthesis of hyaluronate and demineralization persisted for at least 24 h more. When calcitonin was added to bones which were treated with parathormone, the parathormone-induced inhibition of citrate metabolism did not change, but both hyaluronate synthesis and demineralization rapidly declined. Subsequently the rate of hyaluronate synthesis increased, and this was followed several hours later by an increase in demineralization. These data suggest that citrate and hyaluronate metabolism are involved in the overall response of bone to parathormone but are only loosely coupled to one another. Synthesis of hyaluronate appears to be more closely related to subsequent calcium release than is citrate metabolism.
D000818:Animals; D001862:Bone Resorption; D001842:Bone and Bones / Q000378:metabolism*; D002116:Calcitonin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002951:Citrates / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005944:Glucosamine / Q000378:metabolism; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D007700:Kinetics; D051379:Mice; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats
D002951:Citrates; D010281:Parathyroid Hormone; D006820:Hyaluronic Acid; D002116:Calcitonin; D005944:Glucosamine; D002118:Calcium