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Inhibitory effect of saliva on osteoclastogenesis in vitro requires toll-like receptor 4 signaling.
- Source :
-
Clinical oral investigations [Clin Oral Investig] 2017 Nov; Vol. 21 (8), pp. 2445-2452. Date of Electronic Publication: 2017 Jan 18. - Publication Year :
- 2017
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Abstract
- Objectives: Saliva 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.<br />Material and Methods: To 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.<br />Results: We 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.<br />Conclusion: Inhibition of toll-like receptor 4 signaling revealed that saliva can contribute to innate immunity by preventing hematopoietic progenitors to become osteoclasts.<br />Clinical Relevance: Saliva can activate pattern recognition receptor signaling through endotoxins and other stress factors, indicating the demand for macrophages rather than for osteoclasts.
- Subjects :
- Animals
Biomarkers analysis
Cell Culture Techniques
Female
Humans
In Vitro Techniques
Mice
Mice, Inbred BALB C
Signal Transduction
Tartrate-Resistant Acid Phosphatase
Titanium pharmacology
Bone Marrow Cells physiology
Osteoclasts physiology
Osteogenesis physiology
Saliva physiology
Sulfonamides pharmacology
Toll-Like Receptor 4 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1436-3771
- Volume :
- 21
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Clinical oral investigations
- Publication Type :
- Academic Journal
- Accession number :
- 28101679
- Full Text :
- https://doi.org/10.1007/s00784-016-2041-7