Inhibitory effect of saliva on osteoclastogenesis in vitro requires toll-like receptor 4 signaling

Müller, Heinz-Dieter; Caballé Serrano, Jordi; Lussi, Adrian; Gruber, Reinhard (2017). Inhibitory effect of saliva on osteoclastogenesis in vitro requires toll-like receptor 4 signaling. Clinical oral investigations, 21(8), pp. 2445-2452. Springer-Verlag 10.1007/s00784-016-2041-7

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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. 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. 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. CONCLUSION Inhibition 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > School of Dental Medicine > Department of Oral Surgery and Stomatology
04 Faculty of Medicine > School of Dental Medicine
04 Faculty of Medicine > School of Dental Medicine > Department of Preventive, Restorative and Pediatric Dentistry

UniBE Contributor:

Müller, Heinz-Dieter; Caballé Serrano, Jordi; Lussi, Adrian and Gruber, Reinhard

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1432-6981

Publisher:

Springer-Verlag

Language:

English

Submitter:

Hendrik Meyer-Lückel

Date Deposited:

23 Jul 2019 15:35

Last Modified:

23 Jul 2019 15:35

Publisher DOI:

10.1007/s00784-016-2041-7

PubMed ID:

28101679

Uncontrolled Keywords:

Dentistry Endotoxin Murine bone marrow Osteoclast Saliva Toll-like receptor

BORIS DOI:

10.7892/boris.122918

URI:

https://boris.unibe.ch/id/eprint/122918

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