IL-3, a haematopoiesis regulatory factor, has previously been shown to inhibit both mouse and human osteoclast differentiation and bone resorption. Here, the role of rat IL-3 on rat osteoclast differentiation was evaluated to address whether the inhibitory action of IL-3 on osteoclastogenesis is conserved in various species. It was observed that IL-3 inhibited rat osteoclast differentiation induced by both TNF-α and receptor activator of NF-κB ligand (RANKL). TNF-α is known to induce bone loss in postmenopausal osteoporotic women and it also synergise with many pro-osteoclastogenic cytokines to cause huge pathological bone loss. Importantly, it was found that rat IL-3 inhibits the synergistic action of TNF-α with RANKL and IL-1β, TGF-β1 and TGF-β3. IL-3 downregulates the TNF-α-induced nuclear translocation of NF-κB-p65 and c-fos without affecting c-jun. Interestingly, we observed that IL-3 also inhibits osteoclast differentiation in vivo in rats induced by TNF-α. All these results suggest that inhibitory action of IL-3 on osteoclastogenesis is conserved in various species including mice, rats and humans. Thus, our results clearly indicate that IL-3 has therapeutic potential to treat pathological bone loss in important skeletal diseases.
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Receptor activator of NF-κB ligand
Mesenchymal stem cells
Macrophage colony-stimulating factor
Minimal essential medium-alpha modification
Tartrate-resistant acid phosphatase
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VP is the recipient of a Senior Research Fellowship from the University Grant Commission, New Delhi, India.
This work was supported by the intramural grant from National Centre for Cell Science, Pune.
The Institutional Animal Ethics Committee approved all animal protocols.
Corresponding editor: Dipankar Nandi
Corresponding editor: Dipankar Nandi
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Piprode, V., Singh, K., Kumar, A. et al. IL-3 inhibits rat osteoclast differentiation induced by TNF-α and other pro-osteoclastogenic cytokines. J Biosci 46, 63 (2021). https://doi.org/10.1007/s12038-021-00181-3