Interleukin-4 modulates osteoclast differentiation and inhibits the formation of resorption pits in mouse osteoclast cultures.
Interleukin-4 (IL-4) is a well known lymphocyte growth factor, but it may also modulate the activity of other cell types. In the present study we show that IL-4 exerts a potent dose-dependent inhibitory effect on the resorptive activity of mouse bone cells, measured as the number of resorption pits (decreased down to 14% of control, p < 0.001) or the total resorbed area (down to 20% of control, p < 0.001). The results obtained in bone marrow and unfractionated bone cell cultures indicate that such an effect is mainly due to an inhibition of osteoclast precursors differentiation, rather than to a reduced activity of mature osteoclasts, and is not mediated by the IL-4-induced release of other soluble inhibitory factors. Likewise, although IL-4 may stimulate M-CSF expression, its inhibitory effect on osteoclast recruitment was not prevented by anti-M-CSF antibodies, suggesting that it was not mediated by M-CSF. These results point out IL-4 as an potentially important regulatory factor of osteoclast differentiation.
Riancho
J A
JA
Department of Internal Medicine, Hospital M. Valdecilla, University of Cantabria, Santander, Spain.
Zarrabeitia
M T
MT
Gonzalez-Macias
J
J
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001854:Bone Marrow Cells; D001862:Bone Resorption / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D015847:Interleukin-4 / Q000494:pharmacology*; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology*
D000906:Antibodies; D011994:Recombinant Proteins; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor