Transient expression of M-CSF is important for osteoclast-like cell differentiation in a monocytic leukemia cell line

Cells of U937, a human monocytic leukemia cell line, differentiate into macrophages by treatment with 12-o-tetradecanoylphorbol-13-acetate (TPA), whereas cells treated with 1α,25-dihydroxyvitamin D3 [1,25-(OH)₂D₃] continue to grow without undergoing differentiation. When U937 cells were successively treated with TPA and 1,25-(OH)₂D₃, tartrate-resistant acid phosphatase-positive multinucleated cells appeared at 5 days after the treatment. These osteoclast-like cells released a soluble form of ⁴⁵Ca from ⁴⁵Ca-labeled bone particles. These cells were not formed when the order of treatment with TPA and 1,25-(OH)₂D₃ was reversed. Use of either dexamethasone or interferon-γ (IFN-γ) was effective in inhibiting the formation of these osteoclast-like cells. The expression of c-src, c-fms, and macrophage colony stimulating factor (M-CSF) was induced by TPA treatment; however, TPA induced M-CSF gene transcription was attenuated by the subsequent addition of 1,25-(OH)₂D₃. Furthermore, both dexamethasone and IFN-γ impaired the attenuation of M-CSF expression, suggesting that the transient expression of M-CSF may be important for the formation of osteoclast-like cells.