ArticleInternational journal of molecular medicine2016
Interleukin-21 promotes osteoclastogenesis in RAW264.7 cells through the PI3K/AKT signaling pathway independently of RANKL.
Article in International journal of molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 37 citations in OpenAlex.
- Isonardosinone suppresses osteoclastogenesis through TRAF2/TRAF6-mediated disruption of calcium signaling and coordinate inhibition of MAPK/NF-κB pathways.BBA advances · 2025Article
- Research progress of targeted therapy regulating Th17/Treg balance in bone immune diseases.Frontiers in immunology · 2024Review
- Mechanistic insight of interleukin-9 induced osteoclastogenesis.Immunology · 2023Article
- Serpinb1a suppresses osteoclast formation.Biochemistry and biophysics reports · 2021Article
- Effect of interleukin-6, -17, -21, -22, and -23 and STAT3 on signal transduction pathways and their inhibition in autoimmune arthritis.Immunologic research · 2021Review
- Signaling pathways in human osteoclasts differentiation: ERK1/2 as a key player.Molecular biology reports · 2021Article
- The calcium channel TRPV6 is a novel regulator of RANKL-induced osteoclastic differentiation and bone absorption activity through the IGF-PI3K-AKT pathway.Cell proliferation · 2021Article
- Article
- Gliclazide reduced oxidative stress, inflammation, and bone loss in an experimental periodontal disease model.Journal of applied oral science : revista FOB · 2019Article
- Glucagon-like peptide 2 decreases osteoclasts by stimulating apoptosis dependent on nitric oxide synthase.Cell proliferation · 2018Article
- Anti-inflammatory and anti-angiogenic activities in vitro of eight diterpenes from Daphne genkwa based on hierarchical cluster and principal component analysis.Journal of natural medicines · 2018Article
- Autoantibodies against interleukin-21 correlate with disease activity in patients with rheumatoid arthritis.Clinical rheumatology · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytokines play a key role in the bone destruction of rheumatoid arthritis (RA). Interleukin-21 (IL-21) promotes osteoclastogenesis in RA in a receptor activator of nuclear factor-κB ligand (RANKL)-dependent way. Whether IL-21 is capable of promoting osteoclastogenesis directly in the absence of RANKL remains unknown. In the present study, we examined the osteoclastogenic activity of IL-21 in RAW264.7 cells in the absence of RANKL. We found that IL-21 enhanced osteoclastogenesis and this was demonstrated by increased numbers of tartrate-resistant acid phosphatase (TRAP)-positive stained, multinucleated cells compared with the negative control. Western blot analysis and immunocytochemistry showed the positive expression of calcitonin receptor (CTR) in the IL-21 group. RT-PCR and RT-qPCR also verified the increased mRNA expression of CTR and cathepsin K in the IL-21 group compared with the negative control. The scanning electronic microscope images showed a few resorption pits on the bone slices cultured with IL-21. The phosphoinositide 3-kinase (PI3K)/AKT pathway inhibitor LY294002 significantly suppressed IL-21-induced osteoclastogenesis. Taken together, these findings suggest that IL-21 has direct osteoclastogenic potential independently of RANKL. IL-21 may promote osteoclastogenesis through the PI3K/AKT signaling pathway. Therapy targeting IL-21 may be of value in preventing bone erosions in patients with RA.
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