The importance of parathyroid hormone in inhibition of collagen synthesis and mitogenesis of osteoblastic cell.
Loss of bone substance is a common manifestation of hyperparathyroidism. This suggests that parathyroid hormone (PTH) plays an important role as to bone mass. To investigate the mechanism underlying this change in bone mass, I studied the effects of PTH on collagen synthesis and mitogenesis of UMR-106 rat osteoblastic osteosarcoma cells. PTH inhibits the mitogenesis of UMR-106 rat osteosarcoma cells, the half-maximal concentration being 10(-8) to 10(-7) M, which is similar to the EC50 for cyclic AMP accumulation. Cyclic AMP, whose intracellular concentration was increased by PTH, plays a role in the modulation of mitogenesis, as shown by the comparable inhibitory effects of 8-bromoadenosine-3',5'-cyclic AMP (10(-4) M), forskolin (10(-7) M), and the phosphodiesterase inhibitor, IBMX (10(-5) M). PTH, in a similar concentration range, directly inhibited collagen synthesis. Concurrent with the suppression of collagen synthesis, the amounts of a1(I) and a2(I) collagen mRNA decreased proportionately. The results show that PTH modulates collagen synthesis at the transcriptional level. I concluded that parathyroid hormone inhibits the mitogenesis of osteoblasts as well as collagen synthesis by these cells. The decreases in the number of osteoblasts and the amount of collagen synthesis contribute to the loss of bone substance in hyperparathyroidism.
Pun
K K
KK
Department of Medicine, University of Hong Kong.
D000818:Animals; D002417:Cattle; D003094:Collagen / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000378:metabolism; D008938:Mitosis; D010006:Osteoblasts / Q000378:metabolism*; D012516:Osteosarcoma / Q000473:pathology; D010281:Parathyroid Hormone / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
D010281:Parathyroid Hormone; D012333:RNA, Messenger; D003094:Collagen; D000242:Cyclic AMP