MACROPHAGE-COLONY-STIMULATING FACTOR RELEASE AND RECEPTOR EXPRESSION IN BONE-CELLS

Colony-stimulating factors (CSF) may play a role in bone resorption. T o examine whether osteoblasts secrete colony-stimulating activity (CSA ) in response to parathyroid hormone (PTH) and parathyroid hormone-rel ated peptide (PTHrP), conditioned medium (CM) from ROS 17/2.8 cells an d primary rat osteoblasts were examined for induction of clonal growth of cultured rat bone marrow cells. Untreated cells constitutively sec reted CSA, which increased with PTH and PTHrP treatment. The colonies formed were principally comprised of macrophages, and preincubation of CM with antiserum to murine macrophage colony-stimulating factor (M-C SF) neutralized most of the CSA, suggesting that the osteoblast-derive d CSA was predominantly due to M-CSF. PTHrP treatment upregulated stea dy-state M-CSF mRNA levels. To investigate a paracrine role for M-CSF in bone we examined bone tissue and cells for the M-CSF receptor c-fms using immunohistochemical techniques and demonstrated staining of mat ure osteoclasts both in situ and after isolation. We conclude that M-C SF is responsible for the majority of the CSA released by PTH- and PTH rP-treated rat osteoblasts. In addition we identified CSF-1 receptor e xpression in mature osteoclasts. These data suggest that M-CSF is a me diator of osteoblast-osteoclast interaction in PTH- and PTHrP-induced bone resorption.