Reference : Further insights in the mechanisms of interleukin-1beta stimulation of osteoprotegerin i...
Scientific journals : Article
Human health sciences : Rheumatology
http://hdl.handle.net/2268/3690
Further insights in the mechanisms of interleukin-1beta stimulation of osteoprotegerin in osteoblast-like cells
English
Lambert, Cécile [Université de Liège - ULg]
Oury, Cécile mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Génétique générale et humaine >]
Dejardin, Emmanuel [Université de Liège - ULg]
Chariot, Alain mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Piette, Jacques mailto [Université de Liège - ULg]
Malaise, Michel mailto [Université de Liège - ULg > Département des sciences cliniques > Rhumatologie >]
Merville, Marie-Paule mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Franchimont, Nathalie [Université de Liège - ULg]
Sep-2007
Journal of Bone and Mineral Research
American Society for Bone and Mineral Research
22
9
1350-1361
Yes (verified by ORBi)
International
0884-0431
1523-4681
Washington
DC
[en] Base Sequence ; Apoptosis ; Blotting, Western ; Cell Line, Tumor ; DNA Primers ; Enzyme Activation ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-1beta/pharmacology ; Mitogen-Activated Protein Kinases/metabolism ; Osteoprotegerin/biosynthesis/pharmacology ; RNA, Small Interfering ; Reverse Transcriptase Polymerase Chain Reaction
[en] The mechanisms of IL-1beta stimulation of OPG were studied in more detail. Whereas p38 and ERK activation was confirmed to be needed, NF-kappaB was not necessary for this regulation. We also found that OPG production after IL-1beta stimulation was not sufficient to block TRAIL-induced apoptosis in MG-63 cells. INTRODUCTION: Osteoprotegerin (OPG) plays a key role in the regulation of bone resorption and is stimulated by interleukin (IL)-1beta. Herein, we defined the mechanisms of IL-1beta stimulation of OPG focusing on the potential involvement of MAPK and NF-kappaB. We also examined whether OPG production in response to IL-1beta influences TRAIL-induced apoptosis in MG-63 cells. MATERIALS AND METHODS: OPG mRNA levels in MG-63 cells were quantified by real-time RT-PCR and protein levels of OPG and IL-6 by ELISA. Cell viability was assessed using the methyltetrazidium salt (MTS) reduction assay. The role of the MAPK pathway was studied by both Western blotting and the use of specific chemical inhibitors. NF-kappaB function was studied using BAY 11-7085 and by siRNA transfection to inhibit p65 synthesis. Transcription mechanisms were analyzed by transiently transfecting MG-63 cells with OPG promoter constructs. Post-transcriptional effects were examined by using cycloheximide and actinomycin D. RESULTS: MG-63 cells treatment with IL-1beta resulted in the phosphorylation of c-Jun NH(2)-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK). The use of the specific inhibitors showed that p38 and ERK but not JNK were needed for IL-1beta-induced OPG production. In contrast, NF-kappaB was not essential for IL-1beta induction of OPG. We also showed a small transcriptional and a possible post-transcriptional or translational regulation of OPG by IL-1beta. Exogenous OPG blocked TRAIL-induced apoptosis, but IL-1beta induction of OPG did not influence TRAIL-induced cell death. CONCLUSIONS: IL-1beta stimulates OPG production by mechanisms dependent on p38 and ERK. In contrast, NF-kappaB was not essential for this regulation. Although the relevance of IL-1beta stimulation of OPG is still not fully understood, our data showed that IL-1beta stimulation of OPG does not modify TRAIL-induced cell death.
Giga-Signal Transduction
FNRS, TELEVIE, ARC ULG, CHU
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/3690
also: http://hdl.handle.net/2268/56796
10.1359/jbmr.070508

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