Work

Runt-related transcription factor 2 transcriptionally represses sirtuin 1 to regulate osteoclastogenesis and tooth eruption.

Year: 2026

Type: article

Abstract: Background/purpose: Cleidocranial dysplasia (CCD), caused by Runt-related transcription factor 2 (RUNX2) haploinsufficiency, features delayed tooth eruption. Although impaired osteoclastogenesis contributes to eruption failure, the direct molecular mechanisms linking RUNX2 deficiency to osteoclast dysfunction remain elusive. Sirtuin 1 (SIRT1) is a critical regulator of osteoclastogenesis; however, whether it serves as a downstream effector of RUNX2 remains unexplored. This study aimed to elucidate the mechanistic link between RUNX2 and SIRT1 in regulating osteoclast differentiation and tooth eruption. Materials and methods: mice were transfected with small interfering RNA targeting SIRT1 for rescue experiments. Osteoclast differentiation and function were assessed by tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assays. Results: cells. Conclusion: RUNX2 haploinsufficiency impairs tooth eruption through transcriptional derepression of SIRT1, which inhibits osteoclastogenesis via NF-κB p65 deacetylation, highlighting the RUNX2-SIRT1 axis as a novel therapeutic target for CCD.

Source: PubMed

DOI: 10.1016/j.jds.2025.07.3510