1,25 dihydroxyvitamin D3 stimulates differentiation of committed murine bone marrow-derived macrophage precursor cells.
1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] and macrophage colony-stimulating factor (M-CSF) both accelerate differentiation of marrow macrophages from which osteoclasts are derived. Previously, we showed that the steroid's effect on early macrophage precursors may be mediated through M-CSF, as the steroid enhances cytokine receptor expression. In contrast, 1,25-(OH)2D3 blunts M-CSF receptor expression on more mature, yet still pluripotential, hematopoietic precursors. Extending these observations to marrow cells committed to macrophage differentiation, we found that 1,25-(OH)2D3 causes a marked decrease in cellular proliferation despite a 2- to 3-fold increase in [125I]M-CSF binding in a similar dose-dependent metabolite-specific manner. Scatchard analysis demonstrated that increased binding reflects increased receptor capacity without an alteration in affinity. Steroid-induced M-CSF receptor enhancement reflects acceleration of protein appearance rather than overexpression, as treated and untreated cells ultimately exhibit equivalent binding. Increased M-CSF receptor expression is mirrored by increased c-fms messenger RNA levels, and actinomycin D or cycloheximide experiments indicate that new receptor synthesis, rather than mobilization of intracellular pools, is required. Thus, 1,25-(OH)2D3 differentially impacts on M-CSF receptor expression throughout the spectrum of bone marrow macrophage differentiation.
Perkins
S L
SL
Department of Pathology, University of Utah Health Sciences, Salt Lake City 84132, USA.
Kling
S J
SJ
Ross
F P
FP
Teitelbaum
S L
SL
D000818:Animals; D001854:Bone Marrow Cells; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D013234:Stem Cells / Q000187:drug effects*
D016186:Receptor, Macrophage Colony-Stimulating Factor; D002117:Calcitriol