IL-3 inhibits rat osteoclast differentiation induced by TNF-α and other pro-osteoclastogenic cytokines

• Published in: Journal of biosciences 2021-09, Vol.46 (3), Article 63
• Main Authors: Piprode, Vikrant, Singh, Kanupriya, Kumar, Anil, Joshi, Snehal R., Wani, Mohan R.
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedical materials; Biomedicine; Bone loss; Bone resorption; Bones; c-Fos protein; c-Jun protein; Cell Biology; Cell Differentiation; Cytokines; Differentiation; Haemopoiesis; IL-1β; Interleukin 3; Interleukin-3 - physiology; Life Sciences; Mice; Microbiology; NF-kappa B - metabolism; NF-κB protein; Nuclear transport; Osteoclastogenesis; Osteoclasts; Osteogenesis; Osteoporosis; Plant Sciences; Post-menopause; RANK Ligand - metabolism; Rats; Rats, Wistar; Receptors; TRANCE protein; Transcription Factor AP-1 - metabolism; Transcription factors; Transforming growth factor-b1; Translocation; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Women; Zoology
• ISSN: 0250-5991; 0973-7138
• DOI: 10.1007/s12038-021-00181-3

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-β 1 and TGF-β 3 . 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.