THE CELL-SURFACE FORM OF COLONY-STIMULATING FACTOR-I IS REGULATED BY OSTEOTROPIC AGENTS AND SUPPORTS FORMATION OF MULTINUCLEATED OSTEOCLAST-LIKE CELLS

Colony-stimulating factor-1 (CSF-1) is a hematopoietic growth factor t hat is released by osteoblasts and is recognized to play a critical ro le 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 polym erase chain reaction, flow cytometry, and Western immunoblot analysis, we have demonstrated that human osteoblast-like cells as well as prim ary human osteoblasts express the cell-surface form of CSF-1 both cons titutively and in response to parathyroid hormone and tumor necrosis f actor. Furthermore, using an in vitro coculture system, we have shown that cell-surface CSF-1 alone is sufficient to support osteoclast form ation. These findings may be especially significant in view of evidenc e that direct cell-to-cell contact is critical for osteoclast formatio n, and suggest that differential regulation of expression of the CSF-1 isoforms may influence osteoclast function modulated by osteotropic h ormones.