Effect of IL-1beta, PGE(2), and TGF-beta1 on the expression of OPG and RANKL in normal and osteoporotic primary human osteoblasts

The RANKL/RANK/OPG pathway is essential for bone remodeling regulation. Many hormones and cytokines are involved in regulating gene expression in most of the pathway components. Moreover, any deregulation of this pathway can alter bone metabolism, resulting in loss or gain of bone mass. Whether oste...

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Published in:Journal of cellular biochemistry 2010-05, Vol.110 (2), p.304-310
Main Authors: Jurado, Susana, Garcia-Giralt, Natalia, Díez-Pérez, Adolfo, Esbrit, Pedro, Yoskovitz, Guy, Agueda, Lídia, Urreizti, Roser, Pérez-Edo, Lluís, Saló, Guillem, Mellibovsky, Leonardo, Balcells, Susana, Grinberg, Daniel, Nogués, Xavier
Format: Article
Language:English
Subjects:
Case-Control Studies
Cells, Cultured
Dinoprostone - pharmacology
Enzyme-Linked Immunosorbent Assay
Female
Gene Expression Regulation - drug effects
Humans
Interleukin-1beta - pharmacology
Osteoblasts - cytology
Osteoblasts - drug effects
Osteoblasts - metabolism
Osteoporosis - genetics
Osteoprotegerin - genetics
Polymerase Chain Reaction
RANK Ligand - genetics
Transforming Growth Factor beta1 - pharmacology
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Summary:The RANKL/RANK/OPG pathway is essential for bone remodeling regulation. Many hormones and cytokines are involved in regulating gene expression in most of the pathway components. Moreover, any deregulation of this pathway can alter bone metabolism, resulting in loss or gain of bone mass. Whether osteoblasts from osteoporotic and nonosteoporotic patients respond differently to cytokines is unknown. The aim of this study was to compare the effect of interleukin (IL)-1beta, proftaglandin E(2) (PGE(2)), and transforming growth factor-beta1 (TGF-beta1) treatments on OPG and RANKL gene expression in normal (n = 11) and osteoporotic (n = 8) primary osteoblasts. OPG and RANKL mRNA levels of primary human osteoblastic (hOB) cell cultures were assessed by real-time PCR. In all cultures, OPG mRNA increased significantly in response to IL-1beta treatment and decreased in response to TGF-beta1 whereas PGE(2) treatment had no effect. RANKL mRNA levels were significantly increased by all treatments. Differences in OPG and RANKL responses were observed between osteoporotic and nonosteoporotic hOB: in osteoporotic hOB, the OPG response to IL-1beta treatment was up to three times lower (P = 0.009), whereas that of RANKL response to TGF-beta1 was five times higher (P = 0.002) after 8 h of treatment, as compared with those in nonosteoporotic hOBs. In conclusion, osteoporotic hOB cells showed an anomalous response under cytokine stimulation, consistent with an enhanced osteoclastogenesis resulting in high levels of bone resorption.
ISSN:1097-4644
DOI:10.1002/jcb.22538