MODULATION OF OSTEOGENIC CELL ULTRASTRUCTURE BY RS-23581, AN ANALOG OF HUMAN PARATHYROID-HORMONE (PTH)-RELATED PEPTIDE-(1-34), AND BOVINE PTH-(1-34)

RS-23581, a synthetic analog of human PTH-related protein-(1-34), and the amino-terminal 34 amino acids of bovine PTH[bPTH-(1-34)] increase bone mineral density. We wished to determine how quickly the ultrastru cture of the osteogenic cells, i.e. osteoblasts and lining cells, of t he cancellous bone of the second lumbar vertebra of ovariectomized rat s was altered in response to the initiation and cessation of treatment . Ovariectomized rats were injected daily with 80 mu g/kg RS-23581, bP TH-(1-34), or vehicle for 19 days. Animals were killed throughout the treatment period and during the ensuing 10 days. By 5 days after the i nitiation of treatment with either peptide, the cells on the trabecula r surface were predominantly (>90%) osteoblasts, with only a small inc rease in the total cell number. Throughout the dosing period, the rela tive area of the cytoplasm of osteogenic cells from rats treated with RS-23581 or bPTH-(1-34) was greater than that of cells from the ovarie ctomized control group, suggesting a relationship between bone formati on and cytoplasmic mass. By 7 days after the cessation of treatment, t he trabecular surface was covered predominantly by lining cells withou t a change in cell number. Thus, these peptides apparently promote the differentiation of lining cells to osteoblasts and maintain the osteo blast phenotype; the osteoblasts revert to lining cells after the pept ides are withdrawn.