DNA damage‐inducible transcript 3 deficiency promotes bone resorption in murine periodontitis models.
Background and Objective: Periodontitis is a multifactorial inflammatory disease that leads to the destruction of supporting structures of the teeth. DNA damage‐inducible transcript 3 (DDIT3) plays crucial roles in cell survival and differentiation. DDIT3 regulates bone mass and osteoclastogenesis i...
| Publicado en: | Journal of Periodontal Research Vol. 58; no. 4; pp. 841 - 852 |
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| Autores principales: | , , , , , |
| Formato: | diagnostic images pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Aug2023
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=164722919&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 164722919 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00223484 8E9 jtl: Journal of Periodontal Research issn: 00223484 maglogo: Y pubinfo: dt: Aug2023 vid: 58 iid: 4 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 164722919 163903117 164722919 164722919 10.1111/jre.13142 164722919 ppf: 841 ppct: 11 formats: tig: atl: DNA damage‐inducible transcript 3 deficiency promotes bone resorption in murine periodontitis models. aug: au: Luo, Yao Yang, Beining Dong, Wei Yu, Wenqian Jia, Meie Wang, Jiawei affil: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‐MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China sug: subj: Periodontitis Complications Bone Resorption Risk Factors Transcription Factors Deficiency Transcription Factors Physiology Animal Studies Models, Biological Mice Clustered Regularly Interspaced Short Palindromic Repeats Gene Expression Periodontium Metabolism Polymerase Chain Reaction Immunohistochemistry Alveolar Process Phenotype Tomography, X-Ray Computed Methods Microscopy Osteoclasts Physiology Histology Staining and Labeling Osteoclasts Metabolism Acid Phosphatase Analysis Macrophages Analysis Inflammation Risk Factors Osteogenesis Alveolar Bone Loss Risk Factors Cytokines Metabolism Biological Markers Metabolism In Vitro Studies Funding Source ab: Background and Objective: Periodontitis is a multifactorial inflammatory disease that leads to the destruction of supporting structures of the teeth. DNA damage‐inducible transcript 3 (DDIT3) plays crucial roles in cell survival and differentiation. DDIT3 regulates bone mass and osteoclastogenesis in femur. However, the role of DDIT3 in periodontitis has not been elucidated. This research aimed to explore the role and mechanisms of DDIT3 in periodontitis. Methods: DDIT3 gene knockout (KO) mice were generated using a CRISPR/Cas9 system. Experimental periodontitis models were established to explore the role of DDIT3 in periodontitis. The expression of DDIT3 in periodontal tissues was detected by quantitative real‐time polymerase chain reaction (qRT‐PCR) and immunohistochemistry (IHC). The alveolar bone phenotypes were observed by micro‐CT and stereomicroscopy. The inflammation levels and osteoclast activity were examined by histological staining, immunostaining, and qRT‐PCR. Bone marrow‐derived macrophages (BMMs) were isolated to confirm the effects of DDIT3 on osteoclast formation and function in vitro. Results: The increased expression of DDIT3 in murine inflamed periodontal tissues was detected. DDIT3 knockout aggravated alveolar bone loss and enhanced expression levels of inflammatory cytokines in murine periodontitis models. Increased osteoclast formation and higher expression levels of osteoclast‐specific markers were observed in the inflamed periodontal tissues of KO mice. In vitro, DDIT3 deficiency promoted the formation of tartrate‐resistant acid phosphatase (TRAP)‐positive multinucleated osteoclasts and the bone resorption activity of mature osteoclasts. Conclusions: Our results demonstrate that DDIT3 deletion aggravated alveolar bone loss in experimental periodontitis through enhanced inflammatory reactions and osteoclastogenesis. The anti‐inflammation and the inhibition of bone loss by DDIT3 in murine periodontitis provides a potential novel therapeutic strategy for periodontitis. pubtype: Academic Journal doctype: diagnostic images pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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