ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Soluble RANKL Cleaved from Activated Lymphocytes by TNF-α-Converting Enzyme Contributes to Osteoclastogenesis in Periodontitis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 70 citations in OpenAlex.
- Interleukin-38 promotes alveolar bone repair in periodontitis by suppressing the nuclear factor kappa B pathway.Stem cell research & therapy · 2026Article
- A Pre-Clinical Model of Synovitis Using Ex vivo Human Synovial Tissue with Preserved Function and Architecture.Journal of visualized experiments : JoVE · 2026Article
- Dual probiotic intervention with Lactiplantibacillus plantarum Kmiate-6 and Pediococcus acidilactici Kmiate-15 improves periodontal health and oral microbiota balance in dogs.Animal microbiome · 2026Article
- Inhibition of membrane RANKL production in osteoblasts mediates curcumin-inhibited osteoclastogenesis.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · 2026Article
- Effects of Subcutaneous Administration of Glucocorticoids by Pellets on a Mouse Model of Ligature-Induced Periodontal Disease.Journal of clinical medicine · 2025Article
- Resident synovial macrophages in synovial fluid: Implications for immunoregulation.Clinical immunology (Orlando, Fla.) · 2025Article
- The Effects and Mechanisms of Patchouli Alcohol on Experimental Periodontitis Rats Based on the OPG/RANK/RANKL/P38 MAPK Signaling Pathway.Journal of inflammation research · 2025Article
- Inflammation and mechanical force-induced bone remodeling.Periodontology 2000 · 2024Review
- Correlation between systemic immune-inflammatory index and graded diagnosis of periodontitis: a combined cross-sectional and retrospective study.BMC oral health · 2024Article
- Effects of IL-34 and anti-IL-34 neutralizing mAb on alveolar bone loss in a ligature-induced model of periodontitis.Molecular oral microbiology · 2024Article
- Association between the systemic immune inflammation index and periodontitis: a cross-sectional study.Journal of translational medicine · 2024Article
- Unveiling sex-disparities and the impact of gender-affirming hormone therapy on periodontal health.Frontiers in dental medicine · 2024Review
- Regulation of the Osteocyte Secretome with Aging and Disease.Calcified tissue international · 2023Review
- Soluble Sema4D cleaved from osteoclast precursors by TACE suppresses osteoblastogenesis.Journal of cellular and molecular medicine · 2023Article
- Wnt Signaling Activation in Gingival Epithelial Cells and Macrophages of Experimental Periodontitis.Dentistry journal · 2023Article
- Assessment of Periodontal Health Among Removable and Fixed Partial Denture Wearers in Aseer Region of Saudi Arabia.Medical science monitor : international medical journal of experimental and clinical research · 2023Article
- Identification of a binding site on soluble RANKL that can be targeted to inhibit soluble RANK-RANKL interactions and treat osteoporosis.Nature communications · 2022Article
- Molecular Mechanisms Leading from Periodontal Disease to Cancer.International journal of molecular sciences · 2022Review
- Effects of submucosally administered platelet-rich plasma on the rate of tooth movement.The Angle orthodontist · 2022Article
- Immunomodulatory role of metalloproteinase ADAM17 in tumor development.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 5 countries.
Funding
Abstract
Host immune responses play a key role in promoting bone resorption in periodontitis via receptor activator of NF-κB ligand (RANKL)-dependent osteoclastogenesis. Both membrane-bound RANKL (mRANKL) expressed on lymphocytes and soluble RANKL (sRANKL) are found in periodontal lesions. However, the underlying mechanism and cellular source of sRANKL release and its biological role in periodontitis are unclear. TNF-α-converting enzyme (TACE) is reported to cleave the following: 1) precursor TNF-α with release of mature, soluble TNF-α and 2) mRANKL with release of sRANKL. Both soluble TNF-α and sRANKL are found in the periodontitis lesion, leading to the hypothesis that TACE expressed on lymphocytes is engaged in RANKL shedding and that the resulting sRANKL induces osteoclastogenesis. In the current study, upon stimulating PBLs with mitogens in vitro, RANKL expression, sRANKL secretion, and TACE expression were all upregulated. Among the four putative mRANKL sheddases examined in neutralization assays, TACE was the only functional sheddase able to cleave mRANKL expressed on PBL. Moreover, PBL culture supernatant stimulated with mitogens in the presence of anti-TACE Ab or anti-RANKL Ab showed a marked reduction of osteoclastogenesis from osteoclast precursors, indicating that TACE-mediated sRANKL may possess sufficient osteoclastogenic activity. According to double-color confocal microscopy, B cells expressed a more pronounced level of RANKL and TACE expression than T cells or monocytes in periodontally diseased gingiva. Conditioned medium of patients' gingival lymphocyte culture increased in vitro osteoclastogenic activity, which was suppressed by the addition of anti-TACE Ab and anti-RANKL Ab. Therefore, TACE-mediated cleavage of sRANKL from activated lymphocytes, especially B cells, can promote osteoclastogenesis in periodontitis.
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Registered trials
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