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1.
Biology (Basel) ; 10(11)2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34827196

RESUMO

Irradiation of facial bones is associated with a lifelong risk of osteonecrosis. In a rat model, maxillae were exposed to a single 5 Gy dose of external beam radiation and orthodontic force was applied for 2 weeks on the first maxillary molar; control rats were treated identically without radiation. Tooth movement in irradiated jaws was 30% less than in controls, representing radiation-related damage. Micro-CT, histological, and molecular outcomes of orthodontic tooth movement were studied. Microstructurally, bone parameters (trabecular thickness, bone volume fraction, bone mineral density) were significantly affected by orthodontic force but not by radiation. Histological parameters were influenced only by orthodontic force, especially by an increase in osteoclasts. A molecular study revealed a differential distribution of cells expressing pre-osteoclast markers (RANK+-majority, CD11b+, CD14+-minority), with changes being influenced by orthodontic force (increased CD11b+ and CD14+ cells) and also by radiation (decreased RANK+ cells). The activation status of osteoclasts (TRAP staining) showed an orthodontic-force-related increase, which probably could not fully compensate for the radiation-associated impairment. The overall balance showed that orthodontic force had elicited a substantial microstructural, histological, and functional normalization process in irradiated maxillae but a radiation-induced impact was still conspicuous. Additional studies are needed to validate these findings.

2.
Cell Rep ; 14(6): 1462-1476, 2016 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-26854224

RESUMO

Factors linking inflammation and cancer are of great interest. We now report that the chromatin-targeting E3 ubiquitin ligase RNF20/RNF40, driving histone H2B monoubiquitylation (H2Bub1), modulates inflammation and inflammation-associated cancer in mice and humans. Downregulation of RNF20 and H2Bub1 favors recruitment of p65-containing nuclear factor κB (NF-κB) dimers over repressive p50 homodimers and decreases the heterochromatin mark H3K9me3 on a subset of NF-κB target genes to augment their transcription. Concordantly, RNF20(+/-) mice are predisposed to acute and chronic colonic inflammation and inflammation-associated colorectal cancer, with excessive myeloid-derived suppressor cells (MDSCs) that may quench antitumoral T cell activity. Notably, colons of human ulcerative colitis patients, as well as colorectal tumors, reveal downregulation of RNF20/RNF40 and H2Bub1 in both epithelium and stroma, supporting the clinical relevance of our tissue culture and mouse model findings.


Assuntos
Colite Ulcerativa/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Histonas/genética , NF-kappa B/genética , Ubiquitina-Proteína Ligases/genética , Animais , Cromatina/química , Cromatina/imunologia , Colite Ulcerativa/complicações , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Colo/imunologia , Colo/patologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Histonas/imunologia , Humanos , Inflamação , Masculino , Camundongos , Camundongos Transgênicos , Células Mieloides/imunologia , Células Mieloides/patologia , NF-kappa B/imunologia , Transdução de Sinais , Linfócitos T/imunologia , Linfócitos T/patologia , Transcrição Gênica , Ubiquitina-Proteína Ligases/imunologia , Ubiquitinação
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