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Tumor necrosis factor‐α induces transcription of the colony‐stimulating factor‐1 gene in murine osteoblasts
Author(s) -
Kaplan Daniel L.,
Eielson Charlotte M.,
Horowitz Mark C.,
Insogna Karl L.,
Weir Eleanor C.
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199607)168:1<199::aid-jcp24>3.0.co;2-1
Subject(s) - transcription factor , tumor necrosis factor alpha , tumor necrosis factor α , cancer research , gene , osteoblast , biology , microbiology and biotechnology , necrosis , immunology , genetics , in vitro
Tumor necrosis factor‐α (TNF‐α) stimulates bone resorption both in vitro and in vivo. The cellular mechanisms for this effect are not known but one pathway may be via release of osteoblast derived factors which stimulate osteoclast formation. Because colony‐stimulating factor‐1 (CSF‐1) is essential for osteoclast progenitor proliferation, we examined the effect of TNF‐α on osteoblast expression of CSF‐1. TNF‐α treatment of MC3T3‐E1 or primary mouse osteoblasts stimulated the secretion of an activity that was mitogenic for a CSF‐1 responsive cell line and was completely neutralized by antiserum to CSF‐1. By Northern analysis, TNF‐α caused a dose and time (3 to 24 h) dependent increase in CSF‐1 transcript expression in MC3T3‐E1 cells. mRNA stability studies using actinomycin D revealed that TNF‐α does not affect CSF‐1 mRNA half‐life in MC3T3‐E1 cells, while nuclear‐run off analysis demonstrated that TNF‐α increases CSF‐1 gene transcription. Cycloheximide treatment of MC3T3‐E1 cells up‐regulated CSF‐1 mRNA, and compared to either agent alone, cycloheximide and TNF‐α in combination resulted in augmentation of CSF‐1 expression. A series of studies using both agonists and inhibitors indicated that TNF‐α‐induced CSF‐1 expression did not involve the arachidonic acid, PKC, or cAMP pathways. These results suggest that TNF‐α induces CSF‐1 expression in osteoblasts by a transcriptional mechanism which is largely independent of new protein synthesis and of the second messenger pathways examined. © 1996 Wiley‐Liss, Inc.