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Updated: Jun 5, 2026
Accessing the Cytotoxicity and Cell Response to Biomaterials
Published on: July 8, 2021
OCT4-driven PER1 activation promotes odontogenic differentiation in senescent SCAP spheres
Changfang Li1,2, Zibin Zhang2, Zhuoxin Yang1
1State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, Department of Operative Dentistry and Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
Octamer-binding transcription factor 4 (OCT4) reverses replicative senescence in stem cells from apical papilla (SCAP) by activating period circadian regulator 1 (PER1). This enhances SCAP proliferation and odontogenic differentiation for regenerative medicine.
Area of Science:
- Stem cell biology
- Regenerative medicine
- Molecular mechanisms of aging
Background:
- Mesenchymal stem cells (MSCs) are crucial for regenerative medicine.
- Replicative senescence limits MSC therapeutic potential.
- Understanding senescence reversal is key for clinical applications.
Purpose of the Study:
- To investigate the role of OCT4 in reversing replicative senescence in stem cells from apical papilla (SCAP).
- To elucidate the molecular mechanisms underlying OCT4-mediated senescence reversal.
- To assess the impact of OCT4 on SCAP proliferation and odontogenic differentiation.
Main Methods:
- Overexpression of OCT4 in replicative senescent SCAP spheres.
- Assays for cell cycle arrest, senescence-associated β-galactosidase activity, and senescence markers (CDKN2A/P16, CDKN1A/P21, TP53/P53).
- In vitro proliferation and odontogenic differentiation assays, and in vivo pulp-like tissue regeneration assessment.
Main Results:
- OCT4 overexpression alleviated cell cycle arrest and reduced senescence markers.
- Enhanced proliferation and odontogenic differentiation of SCAP spheres in vitro.
- Promoted regenerative pulp-like tissue formation in vivo.
- OCT4 directly activated PER1 transcription, restoring odontogenic capacity.
Conclusions:
- The OCT4-PER1 axis is a critical pathway counteracting replicative senescence in SCAP.
- Targeting this axis offers novel therapeutic strategies for MSC-based regeneration.
- Reversing senescence in SCAP via OCT4 enhances regenerative potential.
