Parathyroid hormone inhibits collagen synthesis at both ribonucleic acid and protein levels in rat osteogenic sarcoma cells.
Cells of the clonal rat osteogenic sarcoma cell line, UMR 106-01, were used to investigate the regulation of collagen synthesis by PTH in osteoblastic cells. Monolayer cultures of cells were labeled with [3H] proline in order to determine both collagen type and rates of production. Analysis of labeled extracellular polypeptides on sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that UMR 106-01 cells synthesized predominantly type I collagen, accounting for 45.48 +/- 2.09% of the radioactivity incorporated into total protein. After 24-h treatment with bovine PTH (1-34, 10(-8) M), collagen synthesis (i.e. collagenase-digestible protein) was decreased to 29.45 +/- 1.39% of total protein production. This decrease was first observed 12 h after addition of hormone and greatest inhibition was achieved at 24 h. The effect of PTH was dose dependent, with half-maximal inhibition of collagen synthesis occurring at 5 x 10(-10) M after 24-h treatment. In contrast, when steady state levels of mRNA for type I collagen chains were examined by Northern blot analysis, the concentration of PTH that reduced collagen synthesis by 35-45% (10(-8) M), caused a net decrease of approximately 80-96% in the number of procollagen transcripts; a small reduction in beta-actin mRNA levels was also observed. The effect of the hormone on procollagen message level was dose dependent, with significant inhibition observed at 10(-10) M PTH and, as with collagen synthesis, maximal after 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Partridge
N C
NC
Pediatric Research Institute, Cardinal Glennon Children's Hospital, St. Louis, Missouri 63110.
Dickson
C A
CA
Kopp
K
K
Teitelbaum
S L
SL
Crouch
E C
EC
Kahn
A J
AJ
D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis*; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects*; D012313:RNA / Q000235:genetics*; D051381:Rats; D012513:Sarcoma, Experimental / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D010281:Parathyroid Hormone; D012313:RNA; D003094:Collagen