Interleukin-1β Upregulates PTHrP-mRNA Expression and Protein Production and Decreases TGF-β in Normal Human Osteoblast-Like Cells
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Osteoblasts are regulated by complex interactions among systemic hormones, cytokines, and local growth factors. Bone resorption, at the level of the basic multicellular unit, is initiated by stimulation of osteoblast activity. The stimulatory effect of interleukin-1β (IL-1β) on bone resorption has not been fully clarified. We have therefore studied the influence of IL-1β on the local production and secretion of parathyroid hormone-related protein (PTHrP) and transforming growth factor-β (TGF-β) from normal human osteoblast-like cells (hOB cells). Using a quantitative PCR-assay following reverse transcription of RNA, in situ hybridization, and a two-site immunofluorometric assay for PTHrP, we demonstrate that IL-1β in a dose- and time-dependent manner increases PTHrP-mRNA expression and PTHrP-protein secretion. In addition, IL-1β decreased the TGF-β protein concentration in conditioned medium. Our results suggest that the actions of IL-1β on bone may be mediated by novel mechanisms involving both local increase of PTHrP, a potent stimulator of bone resorption, and a decrease of TGF-β, an important anabolic and coupling factor for bone turnover.
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