Tanaka, Urara; Kajioka, Shunichi; Finoti, Livia S; Palioto, Daniela B; Kinane, Denis F; Benakanakere, Manjunatha R (2021). Decitabine Inhibits Bone Resorption in Periodontitis by Upregulating Anti-Inflammatory Cytokines and Suppressing Osteoclastogenesis. Biomedicines, 9(2) MDPI 10.3390/biomedicines9020199
|
Text
biomedicines-09-00199.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (1MB) | Preview |
DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2'-deoxycytidine) (1 mg/kg/day) or vehicle treatment. We evaluated bone resorption, osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) and mRNA expression of anti-inflammatory molecules using cluster differentiation 14 positive (CD14+) monocytes from human peripheral blood. Our data showed that decitabine inhibited bone loss and osteoclast differentiation experimental periodontitis, and suppressed osteoclast CD14+ human monocytes; and conversely, that it increased bone mineralization in osteoblastic cell line MC3T3-E1 in a concentration-dependent manner. In addition to increasing IL10 (interleukin-10), TGFB (transforming growth factor beta-1) in CD14+ monocytes, decitabine upregulated KLF2 (Krüppel-like factor-2) expression. Overexpression of KLF2 protein enhanced the transcription of IL10 and TGFB. On the contrary, site-directed mutagenesis of KLF2 binding site in IL10 and TFGB abrogated luciferase activity in HEK293T cells. Decitabine reduces bone loss in a mouse model of periodontitis by inhibiting osteoclastogenesis through the upregulation of anti-inflammatory cytokines via KLF2 dependent mechanisms. DNA methyltransferase inhibitors merit further investigation as a possible novel therapy for periodontitis.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > School of Dental Medicine > Department of Periodontology 04 Faculty of Medicine > School of Dental Medicine > Periodontics Research |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2227-9059 |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
Doris Burri |
Date Deposited: |
26 Jan 2022 12:29 |
Last Modified: |
26 Jan 2022 12:29 |
Publisher DOI: |
10.3390/biomedicines9020199 |
PubMed ID: |
33671221 |
Uncontrolled Keywords: |
Krüppel-like transcription factor-2 decitabine interleukin-10 periodontal bone-loss periodontitis transforming growth factor beta-1 |
BORIS DOI: |
10.48350/164136 |
URI: |
https://boris.unibe.ch/id/eprint/164136 |
Actions (login required)
 |
Edit item |