Interleukin-1beta 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 basic multicellular unit, is initiated by stimulation of osteoblast activity. The stimulatory effect of interleukin-1beta (IL-1beta) on bone resorption has not been fully clarified. We have therefore studied the influence of IL-1beta on the local production and secretion of parathyroid hormone-related protein (PTHrP) and transforming growth factor-beta (TGF-beta) 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-1beta in a dose- and time-dependent manner increases PTHrP-mRNA expression and PTHrP-protein secretion. In addition, IL-1beta decreased the TGF-beta protein concentration in conditioned medium. Our results suggest that the actions of IL-1beta 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-beta, an important anabolic and coupling factor for bone turnover.
Tsai
J A
JA
Department of Molecular Medicine, Endocrine and Diabetes Unit, Karolinska Hospital L1:02, Karolinska Institutet, S-171-76, Stockholm, Sweden.
Rong
H
H
Torring
O
O
Matsushita
H
H
Bucht
E
E
D001483:Base Sequence; D016723:Bone Remodeling / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007375:Interleukin-1 / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D017077:Culture Media, Conditioned; D017931:DNA Primers; D007375:Interleukin-1; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta