Abstract
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.
Highlights
The precise mechanism whereby osteoblasts mediate osteoclastic bone resorption is unclear
The exact nature of all of these cytokines is unknown, compelling in vivo and in vitro data have emerged to support a role for colony-stimulating factor-1 (CSF-1)1 as an osteoblastderived factor involved in osteoclast formation
CSF-1 is derived from a single-copy gene, there is considerable heterogeneity in protein size and structure due to a combination of alternative mRNA splicing, glycosylation, and proteolytic processing [37]
Summary
345–369 577–600 that primary human osteoblasts and osteoblast-like cells express mRNA and protein species consistent with the cell-surface form of CSF-1, and that expression is regulated by PTH and TNF. We report that the cell-surface form of CSF-1 supports the formation of multinucleated osteoclast-like cells in an in vitro co-culture system
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