The Cell-surface Form of Colony-stimulating Factor-1 Is Regulated by Osteotropic Agents and Supports Formation of Multinucleated Osteoclast-like Cells

Colony-stimulating factor-1 (CSF-1) is a hematopoietic growth factor that is released by osteoblasts and is recognized to play a critical role in bone remodeling in vivo and in vitro . CSF-1 is synthesized as a soluble or cell-surface protein. It is unclear, however, whether human osteoblasts expres...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-02, Vol.273 (7), p.4119-4128
Main Authors: Yao, G Q, Sun, B h, Hammond, E E, Spencer, E N, Horowitz, M C, Insogna, K L, Weir, E C
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Cell Differentiation - physiology
Flow Cytometry
Gene Expression Regulation, Developmental - genetics
Histocytochemistry
Humans
Macrophage Colony-Stimulating Factor - analysis
Macrophage Colony-Stimulating Factor - physiology
Membrane Proteins - metabolism
Mice
Osteoblasts - cytology
Osteoclasts - metabolism
Parathyroid Hormone - pharmacology
RNA, Messenger - analysis
Transfection - genetics
Tumor Necrosis Factor-alpha - pharmacology
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Summary:Colony-stimulating factor-1 (CSF-1) is a hematopoietic growth factor that is released by osteoblasts and is recognized to play a critical role in bone remodeling in vivo and in vitro . CSF-1 is synthesized as a soluble or cell-surface protein. It is unclear, however, whether human osteoblasts express both molecular forms of CSF-1, and whether these isoforms can independently mediate osteoclastogenesis. In the present study, using a combination of quantitative reverse transcriptase polymerase chain reaction, flow cytometry, and Western immunoblot analysis, we have demonstrated that human osteoblast-like cells as well as primary human osteoblasts express the cell-surface form of CSF-1 both constitutively and in response to parathyroid hormone and tumor necrosis factor. Furthermore, using an in vitro co-culture system, we have shown that cell-surface CSF-1 alone is sufficient to support osteoclast formation. These findings may be especially significant in view of evidence that direct cell-to-cell contact is critical for osteoclast formation, and suggest that differential regulation of expression of the CSF-1 isoforms may influence osteoclast function modulated by osteotropic hormones.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.273.7.4119