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J Biosci ; 462021.
Article in English | MEDLINE | ID: mdl-34183475

ABSTRACT

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-ĸB 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-1ß, TGFß1 and TGF-ß3. IL-3 downregulates the TNF-α-induced nuclear translocation of NF-ĸB-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.


Subject(s)
Cell Differentiation , Interleukin-3/physiology , Osteoclasts , Osteogenesis , Animals , NF-kappa B/metabolism , RANK Ligand/metabolism , Rats, Wistar , Transcription Factor AP-1/metabolism , Tumor Necrosis Factor-alpha/metabolism
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