EXPRESSION AND SECRETION OF PARATHYROID HORMONE-RELATED PROTEIN BY HUMAN BONE-DERIVED CELLS IN-VITRO - EFFECTS OF GLUCOCORTICOIDS

We investigated the production of parathyroid hormone-related protein (PTHrP) by cells derived from explants of human bone, Using an immunor adiometric assay (IRMA), PTHrP was detected in conditioned medium from cultures of bone-derived cells from 6 of 7 patients investigated in t his study. PTHrP mRNA was identified in human bone cells using reverse transcriptase-linked polymerase chain reaction (RT-PCR) and by Northe rn analysis. Transcripts for PTHrP were detected in a purified populat ion of alkaline phosphatase positive cells isolated from human bone ma rrow cultures by now cytometry, confirming the expression of PTHrP mRN A by cells of the osteoblastic lineage. Production of PTHrP was inhibi ted by 10(-6) M of the glucocorticoids, prednisolone and desacetylated deflazacort, in a dose-dependent manner. In addition, RT-PCR followed by Southern blot analysis detected a decrease in steady-state PTHrP m RNA in cultures of human bone-derived cells treated with 10(-6) M pred nisolone.