Inhibitory effect of interleukin-4 on osteoclast-like cell formation in mouse bone marrow culture.
Recently, interleukin 4 (IL-4) was reported to inhibit bone resorption in mouse long bone culture. To test the effect of IL-4 on the formation of osteoclast-like cells, we used a mouse bone marrow culture system that formed mononuclear and multinucleated cells with osteoclast characteristics. Recombinant mouse IL-4 dose-dependently inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated cells [TRAP(+)MNC] induced by 1,25(OH)2D3, PTH(1-34) or Interleukin-1 alpha (IL-1 alpha). The minimum effective inhibitory concentration was 0.01 ng/ml, and 1 ng/ml IL-4 completely inhibited TRAP(+)MNC formation. IL-4 also dose-dependently inhibited the formation of tartrate-resistant acid phosphatase-positive mononuclear cells. Treatment of cultures with IL-4 for the first or last 48 h of an 8-day culture period inhibited TRAP(+)MNC formation to the same extent, whereas IFN-gamma and calcitonin suppressed TRAP(+)MNC formation mainly at the early and the late phase, respectively. IL-4, as a macrophage fusion factor, at higher concentrations (0.1-10 ng/ml), increased formation of tartrate-resistant acid phosphatase-negative multinucleated cells [TRAP(-)MNC] with giant macrophage characteristics. The half-maximal concentrations inhibiting TRAP(+)MNC formation and stimulating TRAP(-)MNC formation were 0.05 ng/ml and 2 ng/ml, respectively. These results demonstrate that IL-4 inhibits bone resorption by inhibiting the recruitment of osteoclast precursor and formation of multinucleated osteoclast-like cells, and by stimulating the formation of macrophage polykaryons.
Kasono
K
K
Department of Medicine, Tokyo Women's Medical College, Japan.
Sato
K
K
Sato
Y
Y
Tsushima
T
T
Shizume
K
K
Demura
H
H
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D001862:Bone Resorption; D002116:Calcitonin / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D015726:Giant Cells / Q000187:drug effects; D006651:Histocytochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010281:Parathyroid Hormone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D019379:Teriparatide
D007375:Interleukin-1; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011498:Protein Precursors; D011994:Recombinant Proteins; C043830:interleukin 1 precursor; D019379:Teriparatide; D015847:Interleukin-4; D007371:Interferon-gamma; D002116:Calcitonin; D000135:Acid Phosphatase; D002117:Calcitriol