Interleukin-1 beta upregulates PTHrP-mRNA expression and protein production and decreases TGF-beta in normal human osteoblast-like cells

Osteoblasts are regulated by complex interactions among systemic hormones, cytokines, and local growth factors. Bone resorption, at the level of the b asic multicellular unit, is initiated by stimulation of osteoblast activity . The stimulatory effect of interleukin-1 beta (IL-1 beta) on bone resorpti on has not been fully clarified. We have therefore studied the influence of IL-1 beta on the local production and secretion of parathyroid hormone-rel ated protein (PTHrP) and transforming growth factor-beta (TGF-beta) from no rmal human osteoblast-like cells (hOB cells). Using a quantitative PCR-assa y following reverse transcription of RNA, in situ hybridization, and a two- site immunofluorometric assay for PTHrP, we demonstrate that IL-1 beta in a dose- and time-dependent manner increases PTHrP-mRNA expression and PTHrP protein secretion. In addition, IL-1 beta decreased the TGF-beta protein co ncentration in conditioned medium. Our results suggest that the actions of IL-1 beta on bone may be mediated by novel mechanisms involving both local increase of PTHrP, a potent stimulator of bone resorption, and a decrease o f TGF-beta, an important anabolic and coupling factor for bone turnover.