OCT4-driven PER1 activation promotes odontogenic differentiation in senescent SCAP spheres.

Changfang Li, Zibin Zhang, Zhuoxin Yang, Tingjie Liu, Xiaoning He, Bei Li, Wei Wang

Abstract read

In one paragraph

Article in International journal of oral science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Changfang Li *State 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.

Zibin Zhang *State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Disease, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, China.

Zhuoxin Yang *State 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.

Tingjie LiuState Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Disease, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, China.

Xiaoning HeState Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Disease, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, China.

Bei LiState Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Disease, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, China. libei2021@fmmu.edu.cn.ORCID 0000-0003-0876-2248

Wei WangState 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. weiwang_0510@163.com.ORCID 0000-0001-8527-987X

Funding

Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2021YFA1100600Shaanxi Provincial Science and Technology Department (Science and Technology Department, Shaanxi Province) 2023-ZDLSF-49, 2024SF-GJHX-29

6 · The paper itself

Abstract

Mesenchymal stem cells (MSCs) hold significant promise for applications in regenerative medicine, yet their therapeutic potential is often limited by replicative senescence. Identifying effective strategies to reverse replicative senescence in MSCs and elucidating the underlying molecular mechanisms are essential steps in advancing their clinical use. Here, this study demonstrated that the pluripotency regulator octamer-binding transcription factor 4 (OCT4) promoted odontogenic differentiation by activating period circadian regulator 1 (PER1) in replicative senescent stem cells from apical papilla (SCAP) spheres. Specifically, OCT4 overexpression significantly alleviated cell cycle arrest, reduced senescence-associated β-galactosidase activity, and downregulated the expression of senescence-related markers, including CDKN2A/P16, CDKN1A/P21, and TP53/P53. Moreover, this approach markedly enhanced the proliferation and odontogenic differentiation potential of SCAP spheres in vitro and promoted the formation of regenerative pulp-like tissue in vivo. Mechanistically, we demonstrated that OCT4 transcriptionally activated PER1 through direct binding to its promoter, thereby restoring the odontogenic differentiation capacity of replicative senescent SCAP. Collectively, our findings establish the OCT4-PER1 axis as a critical regulatory pathway that counteracts replicative senescence in SCAP. These insights suggest new therapeutic strategies targeting senescence-associated signaling pathways to enhance MSC-based regenerative outcomes.

Indexed as

Cellular SenescenceDental PapillaMesenchymal Stem CellsOctamer Transcription Factor-3OdontogenesisAnimalsbeta-GalactosidaseCell DifferentiationCell ProliferationCells, CulturedHumansMicebeta-GalactosidaseOctamer Transcription Factor-3POU5F1 protein, human

Identifiers

PMID42236493

DOI10.1038/s41368-026-00444-5

PMCPMC13234415

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LicenceCC BY-NC-ND

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.