Leukemia inhibitory factor suppresses proliferation, alkaline phosphatase activity, and type I collagen messenger ribonucleic acid level and enhances osteopontin mRNA level in murine osteoblast-like (MC3T3E1) cells.
The effect of leukemia inhibitory factor (LIF) on proliferation and phenotypic expression in murine osteoblast-like (MC3T3E1) cells was examined. LIF inhibited the proliferation of these cells by up to 20% and DNA synthesis was inhibited in a dose-dependent manner with an ED50 of about 0.2 ng/ml. The effect of LIF relative to matched controls increased with decreasing serum concentration, reaching 30% inhibition at 0.2% serum. LIF also reduced the stimulatory effects of platelet-derived growth factor and insulin-like growth factor I on DNA synthesis. The inhibition of the DNA synthesis by saturating concentration of transforming growth factor beta was further enhanced by the addition of LIF, suggesting independent pathways for the action of the two growth inhibitors. In addition, LIF reduced alkaline phosphatase activity and the abundance of type I collagen messenger RNA, but increased the level of osteopontin messenger RNA. These findings suggest that LIF may play a role in regulating the function of osteoblasts.
Noda
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M
Department of Bone Biology and Osteoporosis Research, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Vogel
R L
RL
Hasson
D M
DM
Rodan
G A
GA
D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D003094:Collagen / Q000235:genetics*; D004247:DNA / Q000096:biosynthesis; D015870:Gene Expression; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D053495:Osteopontin; D012333:RNA, Messenger / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000235:genetics*; D015291:Transforming Growth Factors / Q000494:pharmacology
D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D015291:Transforming Growth Factors; D003094:Collagen; D004247:DNA; D000469:Alkaline Phosphatase