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Effect of inhibition of Dlx3 on gene expression alteration during alveolar bone healing

ABSTRACT: The alveolar ridge loss and absorption strongly affects the following implantation and prosthodontic treatment. It is a clinical challenge and research hotspot to sustain the alveolar bone mass. Interestingly, the patients affected with Tricho-dento-osseous (TDO) syndrome present high density of skull and jaw bones, and can remain sufficient bone mass after tooth extraction in a long time. The mechanism of this phenomenon is of highly study value. To explore DLX3-the disease-causing gene of TDO syndrome, we constructed the mouse alveolar loss and healing model. After tooth extraction, gelatin sponge with GFP or with adenovirus vector that can suppress the expression of Dlx3 gene was put in normal murine alveolar socket, respectively. RNA sequencing of the alveolar bone of these two groups was performed to explore the downstream molecular alterations.

ORGANISM(S): Mus musculus

PROVIDER: GSE270089 | GEO | 2026/06/01

REPOSITORIES: GEO

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Project description:Periodontal granulation tissue is formed during the wound healing process and contributes to subsequent repair or regeneration. However, periodontitis causes the presence of unwanted mass of persistently inflamed granulation tissues in periodontal osseous defects, are routinely eliminated and discarded for anticipated better treatment outcomes. Nevertheless, the emerging evidence of microbiome and histological profiles strongly encourages further studies on this considerable issue and the potential clinical implications. Here, we collected the granulation tissues from pocket wall via excision (PT) and osseous defect (GT) during periodontal surgery, and those attaching on the extracted root surfaces (RT) and remaining in the extraction sockets (ST) during tooth extraction. Subsequently, these samples were used for histological assessment, 16S rRNA sequencing of intra-tissue microbiome and single-cell sequencing (scRNA-seq). The origin-based distinguishment of granulation tissue was well reflected by the clinical and biological characteristics. Conceivably, the periodontal parameters at the involved teeth of RT and ST were more deteriorated than those of GT and PT, which was also reflected with the enrichment of genera of periodontopathogens like Porphyromonas and the depletion of commensals such as Rothia and Neisseria in RT and ST. Further scRNA-seq revealed higher proportion of mesenchymal stem cells and fibroblasts while fewer natural killer cells in GT than those in both PT and ST, in line with elevated wound healing scores and decreased inflammatory response scores. Pseudotime trajectory analysis demonstrated the apparent differentiation of stroma cells among these tissues. Histological examination exhibited a less extent of inflammatory infiltration and CD4+ and NKG2D+ immunoreaction in GT, as compared to other tissue types. Collectively, these findings show the salubriousness of osseous GT and deleteriousness of socket-originated RT and ST in terms of clinical, microbiome and cellular attributes. This work could facilitate the development of novel strategies for potentiating and enhancing periodontal treatment outcomes.

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Effect of inhibition of Dlx3 on gene expression alteration during alveolar bone healing

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