Tumor necrosis factor-alpha and -beta upregulate the levels of osteoprotegerin mRNA in human osteosarcoma MG-63 cells.
Osteoprotegerin (OPG) is a recently cloned soluble member of the tumor necrosis factor receptor family. OPG has been shown to inhibit osteoclast recruitment by binding to OPG-ligand, an osteoclast differentiating factor on osteoblastic stromal cells, thereby blocking osteoclastogenesis. In this report we have examined the effect of tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor-beta (TNF-beta) on OPG mRNA levels in the human osteosarcoma cell line MG-63. We demonstrate that both TNF-alpha and TNF-beta dose- and time-dependently upregulate the mRNA levels of OPG. The effect is significant at and above 5 pM of TNF-alpha and 1 pM of TNF-beta. The stimulatory effect on OPG mRNA levels in MG-63 cells was detected after 2 hrs of incubation with TNF-alpha or TNF-beta. These data demonstrate that the expression of OPG in osteoblasts, with subsequent effects on osteoclastogenesis, is regulated by TNFs.
Department of Medical Sciences, University of Uppsala, Sweden. Helena.Brandstrom@medicin.uu.se
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H
Brändström
K B
KB
Jonsson
O
O
Vidal
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S
Ljunghall
C
C
Ohlsson
O
O
Ljunggren
D001859:Bone Neoplasms; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007700:Kinetics; D008233:Lymphotoxin-alpha / Q000096:biosynthesis*; D053244:Osteoprotegerin; D012516:Osteosarcoma; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D006023:Glycoproteins; D008233:Lymphotoxin-alpha; D053244:Osteoprotegerin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D014409:Tumor Necrosis Factor-alpha