IL-3 inhibits human osteoclastogenesis and bone resorption through downregulation of c-Fms and diverts the cells to dendritic cell lineage

The Journal of Immunology : Official Journal of the American Association of Immunologists
Navita GuptaMohan R Wani

Abstract

IL-3 is an important cytokine that regulates hematopoiesis and functions as a link between the immune and the hematopoietic system. In this study, we investigated the role and mechanism of IL-3 action on human osteoclast formation and bone resorption using PBMCs. PBMCs differentiate into functional osteoclasts in the presence of M-CSF and receptor activator of NF-kappaB ligand as evaluated by 23c6 expression and bone resorption. We found that IL-3 dose-dependently inhibited formation of 23c6-positive osteoclasts, bone resorption and C-terminal telopeptide of type I collagen, a collagen degradation product. The inhibitory effect of IL-3 on bone resorption was irreversible. To investigate the mechanism of IL-3 action, we analyzed the effect of IL-3 on the receptor activator of NF-kappaB and c-Fms receptors and c-Fos, PU.1, NFAT cytoplasmic 1, and RelB transcription factors essential for osteoclastogenesis. IL-3 significantly inhibited c-Fms and downregulated both PU.1 and c-Fos at both mRNA and protein level. Furthermore, IL-3-treated cells showed increased expression of dendritic cell markers CD1a and CD80 and decreased expression of monocyte/macrophage marker CD14. Interestingly, IL-3 inhibited formation of human osteoclasts de...Continue Reading

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Citations

Dec 25, 2013·The Journal of Experimental Medicine·Jun HiroseSakae Tanaka
Oct 10, 2014·Journal of Dental Research·J Caballé-SerranoR Gruber
Dec 6, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kanupriya SinghMohan R Wani
Nov 14, 2015·Experimental & Molecular Medicine·Eunseo OhYoe-Sik Bae
Oct 16, 2018·Journal of Cellular Biochemistry·Niroshani Surangika Soysa, Neil Alles
Aug 6, 2013·Calcified Tissue International·Sarah E WytheNicole J Horwood
Jan 5, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anil KumarMohan R Wani
Mar 6, 2018·Immune Network·Dulshara Sachini AmarasekaraJaerang Rho
Jan 19, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rupesh K SrivastavaMohan R Wani
May 18, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Supinder KourMohan R Wani
Jul 15, 2017·Stem Cell Research & Therapy·Amruta Barhanpurkar-NaikMohan R Wani
Oct 26, 2020·Molecular Biology Reports·Eliana Rita SanpaoloFrancesco Paolo Cantatore
Feb 2, 2012·Biochemical and Biophysical Research Communications·Amruta P BarhanpurkarMohan R Wani
Jul 1, 2021·Journal of Bone Oncology·Kinjal P BhadreshaRakesh M Rawal

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