ArticleClinical oral investigations2017
Inhibitory effect of saliva on osteoclastogenesis in vitro requires toll-like receptor 4 signaling.
Article in Clinical oral investigations, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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Who cites it
5 citing papers in PubMed, 14 citations in OpenAlex.
- Lipocalin-2 upregulation in hypoxic murine osteocytes enhances RANKL-induced osteoclastogenesis.Scientific reports · 2026Article
- Oral cell lysates reduce osteoclastogenesis in murine bone marrow cultures.Cytotechnology · 2025Article
- Liquid PRF Reduces the Inflammatory Response and Osteoclastogenesis in Murine Macrophages.Frontiers in immunology · 2021Article
- Atorvastatin Upregulates microRNA-186 and Inhibits the TLR4-Mediated MAPKs/NF-κB Pathway to Relieve Steroid-Induced Avascular Necrosis of the Femoral Head.Frontiers in pharmacology · 2021Article
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
Abstract
objectivesSaliva can suppress osteoclastogenesis, but the underlying mechanism has not been discovered yet. Considering that endotoxins suppress osteoclastogenesis in bone marrow cultures and that saliva contains endotoxins, it was reasonable to hypothesize that the impact of saliva on osteoclastogenesis requires toll-like receptor 4 signaling. MATERIAL AND
methodsTo test this hypothesis, we blocked toll-like receptor 4 signaling with TAK-242 in the presence of saliva in murine bone marrow cultures. Osteoclastogenesis was evaluated based on gene expression analysis and histochemical staining for tartrate-resistant acid phosphatase. Resorption was performed on dentine.
resultsWe report that TAK-242 reversed the inhibitory effect of fresh sterile saliva on the formation of multinucleated cells that stained positive for tartrate-resistant acid phosphatase. In line with this finding, TAK-242 increased the expression of the osteoclast functional genes cathepsin K, calcitonin receptor, and tartrate-resistant acid phosphatase in the presence of saliva. TAK-242 also supported the expression of NFATc1, the master regulator of osteoclastogenesis, as well as DC-STAMP and Atp6v0d2, both being cell fusion genes. In support of the hypothesis, depletion of saliva from endotoxin partially reversed the inhibitory effect on osteoclastogenesis. Moreover, salivary pellicle on plastic and titanium did not affect osteoclastogenesis.
conclusionInhibition of toll-like receptor 4 signaling revealed that saliva can contribute to innate immunity by preventing hematopoietic progenitors to become osteoclasts. CLINICAL RELEVANCE: Saliva can activate pattern recognition receptor signaling through endotoxins and other stress factors, indicating the demand for macrophages rather than for osteoclasts.
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