J Immunol 2010,
PMID: 20644169
Gupta, Navita; Barhanpurkar, Amruta P; Tomar, Geetanjali B; Srivastava, Rupesh K; Kour, Supinder; Pote, Satish T; Mishra, Gyan C; Wani, Mohan R
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 derived from blood monocytes and bone marrow cells of osteoporotic individuals. Thus, IL-3 may have therapeutic potential as an antiosteolytic agent in treatment of osteoporosis.
Diseases/Pathways annotated by Medline MESH: Bone Resorption
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Text Mining Data
c-Fms — IL-3: "
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
"
c-Fos — IL-3: "
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
"
NF-kappaB — IL-3: "
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
"
c-Fms ⊣ IL-3: "
IL-3 significantly inhibited c-Fms and downregulated both PU.1 and c-Fos at both mRNA and protein level
"
Manually curated Databases
No curated data.