Impact of DLX3/SAHH axis on osteogenic differentiation of BMSCs in alveolar bone

  • J Oral Biosci. 2025 Jun;67(2):100658. doi: 10.1016/j.job.2025.100658.
Shichen Sun  1 ,  Yuxi Jiang  2 ,  Kang Chen  1 ,  Xinyi Chen  1 ,  Jinyou Chai  1 ,  Haipeng Sun  3
Affiliations
  • 1. Department of Prosthodontics and Implantology, Shenzhen University Affiliated Shenzhen Stomatology Hospital, Shenzhen, 518001, Guangdong Province, China.
  • 2. Department of Stomatology, Shenzhen Longgang Central Hospital, Shenzhen, 518116, Guangdong Province, China; School of Dentistry, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518172, Guangdong Province, China.
  • 3. Department of Prosthodontics and Implantology, Shenzhen University Affiliated Shenzhen Stomatology Hospital, Shenzhen, 518001, Guangdong Province, China. Electronic address: [email protected].
PMID: 40180282 DOI: 10.1016/j.job.2025.100658
Abstract

Objectives: Bone marrow mesenchymal stem cells (BMSCs) promote alveolar bone formation and repair. Distal-less homeobox 3 (DLX3) plays a key regulatory role in BMSC osteogenesis. However, the precise pathway by which it mediates osteogenesis in BMSCs remains unclear. In this study, we investigated the potential epigenetic mechanisms underlying DLX3-mediated BMSCs osteogenesis.

Methods: BMSCs were isolated from the alveolar bone. DLX3 overexpression and knockdown cell lines were established using lentivirus-mediated gene transfer. Osteogenic differentiation was evaluated using Alkaline Phosphatase expression, alizarin red staining, real-time quantitative polymerase chain reaction, western blotting, chromatin immunoprecipitation, RNA immunoprecipitation, and S-adenosyl-homocysteine hydrolase (SAHH) activity measurements.

Results: DLX3 enhanced the osteogenic differentiation of BMSCs, positively regulated SAHH, and enhancer of zeste homolog 2 (EZH2) activity. In addition, the long non-coding RNA H19 (H19) bound to SAHH in BMSCs. DLX3 regulated the expression of H19, and rescue experiments showed that H19 knockdown increased SAHH activity, thereby promoting osteogenic differentiation in the DLX3-overexpression group.

Conclusions: The DLX3/SAHH axis may regulate the activity of EZH2 involved in the osteogenic differentiation of BMSCs.

Keywords
DLX3; EZH2; Epigenetic regulation; Osteogenic differentiation; SAHH.
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