Tumor necrosis factor type alpha (cachectin) stimulates mouse osteoblast-like cells (MC3T3-E1) to produce macrophage-colony stimulating activity and prostaglandin E2.
To elucidate the mechanism of tumor necrosis factor alpha (TNF-alpha)-induced bone resorption, the effects of recombinant human TNF-alpha on mouse osteoblast-like cells (MC3T3-E1) were studied. TNF-alpha stimulated MC3T3-E1 cells to produce prostaglandin E2 (PGE2) and macrophage colony stimulating activity (M-CSA) in a dose-dependent manner. TNF decreased alkaline phosphatase (AL-P) activity of MC3T3-E1 cells. These TNF effects were observed at 1 ng/ml (approximately 6 X 10(-11)M). The inhibitory effect on AL-P activity was reversible and the cell growth of MC3T3-E1 cells was only slightly affected by TNF. These findings suggest that both PGE2 and M-CSA stimulated by TNF-alpha are possibly involved in osteoblast-mediated osteoclastic bone resorption, whereas inhibition of AL-P activity may lead to a decrease in bone formation.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003603:Cytotoxins / Q000494:pharmacology*; D015232:Dinoprostone; D006023:Glycoproteins / Q000494:pharmacology*; D007377:Interleukin-3 / Q000096:biosynthesis*; D007700:Kinetics; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha
D003603:Cytotoxins; D006023:Glycoproteins; D007377:Interleukin-3; D011458:Prostaglandins E; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone