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.

Nyckelord

Bone Neoplasms

Glycoproteins

biosynthesis

Humans

Kinetics

Lymphotoxin-alpha

biosynthesis

Osteoprotegerin

Osteosarcoma

Polymerase Chain Reaction

RNA

Messenger

biosynthesis

Receptors

Cytoplasmic and Nuclear

Receptors

Tumor Necrosis Factor

biosynthesis

Time Factors

Transcription

Genetic

drug effects

Tumor Cells

Cultured

Tumor Necrosis Factor-alpha

pharmacology

Up-Regulation

drug effects

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)