2. Academic Validation
  3. Creatine promotes osteogenic differentiation of dental pulp stem cells via the AMPK-ULK1-autophagy axis

Creatine promotes osteogenic differentiation of dental pulp stem cells via the AMPK-ULK1-autophagy axis

  • Connect Tissue Res. 2025 Feb 11:1-14. doi: 10.1080/03008207.2025.2459243.
Lin Liu 1 2 3,  Zhuangzhuang Chu 2 3 4,  Xiao Han 2 3 5,  Jin Wu 2 3 5,  Kunzhan Cai 2 3 5,  Jiaohong Wang 2 3 5,  Zixiang Guo 2 3 5,  Shan Gao 2 3 5,  Guoqing Li 2 3 5,  Chunbo Tang 2 3 5
Affiliations

Affiliations

  • 1 Department of General Dentistry, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
  • 2 Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China.
  • 3 Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China.
  • 4 Department of Dental Implantology, Linyi People's Hospital, Linyi, China.
  • 5 Department of Dental Implantology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
PMID: 39930963 DOI: 10.1080/03008207.2025.2459243
Abstract

Objective: We aimed to demonstrate the effects of creatine (Cr) on osteogenic differentiation (OD) in HDPSCs.

Materials and methods: HDPSCs were treated with Cr and an inhibitor of Cr transporter. The OD capacity was evaluated by detecting ALP staining and activity, alizarin red staining (ARS), as well as osteogenesis-related protein levels. Transcriptomic Sequencing, western blotting, transmission electron microscopy, immunofluorescence staining, and autophagy-related Protein Marker detection were applied to illustrate the underlying mechanism. Furthermore, the impact of Cr on bone regeneration was investigated in vivo.

Results: We found that 1 mm of Cr effectively enhanced the OD of HDPSCs. The creatine group displayed significantly increased AMPK phosphorylation, overexpressed autophagy-related proteins, enhanced OD, and mineralization capabilities. We also found that ULK1 is the downstream molecule through which AMPK induces cellular Autophagy. In vivo results demonstrated that Cr could increase the new bone formation of periodontitis.

Conclusion: Our research discovered a new AMPK-ULK1-autophagy pathway through which Cr enhances OD in HDPSCs. Cr enhanced HDPSCs-mediated periodontal tissue regeneration in a periodontitis mouse model, providing a theoretical foundation for the study of bone repair in periodontitis.

Keywords

AMPK-ULK1-autophagy axis; Periodontitis; creatine; dental pulp stem cells; osteogenic differentiation.

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