The odontoblastic differentiation of dental mesenchymal stem cells: molecular regulation mechanism and related genetic syndromes

Houwen Pan; Yiling Yang; Hongyuan Xu; Anting Jin; Xiangru Huang; Xin Gao; Siyuan Sun; Yuanqi Liu; Jingyi Liu; Tingwei Lu; Xinyu Wang; Yanfei Zhu; Lingyong Jiang

doi:10.3389/fcell.2023.1174579

The odontoblastic differentiation of dental mesenchymal stem cells: molecular regulation mechanism and related genetic syndromes

Front Cell Dev Biol. 2023 Sep 25:11:1174579. doi: 10.3389/fcell.2023.1174579. eCollection 2023.

Authors

Houwen Pan^{1

2

3

4

5

6}, Yiling Yang^{1

2

3

4

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6}, Hongyuan Xu^{1

2

3

4

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6}, Anting Jin^{1

2

3

4

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6}, Xiangru Huang^{1

2

3

4

5

6}, Xin Gao^{1

2

3

4

5

6}, Siyuan Sun^{1

2

3

4

5

6}, Yuanqi Liu^{1

2

3

4

5

6}, Jingyi Liu^{1

2

3

4

5

6}, Tingwei Lu^{1

2

3

4

5

6}, Xinyu Wang^{1

2

3

4

5

6}, Yanfei Zhu^{1

2

3

4

5

6}, Lingyong Jiang^{1

2

3

4

5

6}

Affiliations

¹ Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
³ National Center for Stomatology, Shanghai, China.
⁴ National Clinical Research Center for Oral Disease, Shanghai, China.
⁵ Shanghai Key Laboratory of Stomatology, Shanghai, China.
⁶ Shanghai Research Institute of Stomatology, Shanghai, China.

Abstract

Dental mesenchymal stem cells (DMSCs) are multipotent progenitor cells that can differentiate into multiple lineages including odontoblasts, osteoblasts, chondrocytes, neural cells, myocytes, cardiomyocytes, adipocytes, endothelial cells, melanocytes, and hepatocytes. Odontoblastic differentiation of DMSCs is pivotal in dentinogenesis, a delicate and dynamic process regulated at the molecular level by signaling pathways, transcription factors, and posttranscriptional and epigenetic regulation. Mutations or dysregulation of related genes may contribute to genetic diseases with dentin defects caused by impaired odontoblastic differentiation, including tricho-dento-osseous (TDO) syndrome, X-linked hypophosphatemic rickets (XLH), Raine syndrome (RS), hypophosphatasia (HPP), Schimke immuno-osseous dysplasia (SIOD), and Elsahy-Waters syndrome (EWS). Herein, recent progress in the molecular regulation of the odontoblastic differentiation of DMSCs is summarized. In addition, genetic syndromes associated with disorders of odontoblastic differentiation of DMSCs are discussed. An improved understanding of the molecular regulation and related genetic syndromes may help clinicians better understand the etiology and pathogenesis of dentin lesions in systematic diseases and identify novel treatment targets.

Keywords: dental mesenchymal stem cells; genetic syndrome; molecular regulation; odontoblastic differentiation; signaling pathway.

Publication types

Review

Grants and funding

This work was supported in part by grants from Fund of Department of Oral and Maxillofacial Surgery (Xi 2022-05); the Interdisciplinary Program of Shanghai Jiao Tong University (YG2023ZD14); the Fundamental Research Funds for the Central Universities; the National Natural Science Foundation of China (82271006, 82101048, 82071083, 81870740, and 81570950); the Natural Science Foundation of Shanghai (21ZR1436900 and 22ZR1436700); the Program of Shanghai Academic/Technology Research Leader (20XD1422300); Clinical Research Plan of SHDC (SHDC2020CR4084); the Cross-disciplinary Research Fund of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine (JYJC201902 and JYJC202116); the Innovation Research Team of High-Level Local Universities in Shanghai (SSMUZLCX20180501); the Research Discipline Fund No. KQYJXK2020 from Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, and College of Stomatology, Shanghai Jiao Tong University; Original Exploration Project of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine (JYYC003); Two-Hundred Talent Project of Shanghai Jiao Tong University School of Medicine; the Biomaterials and Regenerative Medicine Institute Cooperative Research Project Shanghai Jiao Tong University School of Medicine (2022LHB02); the Project of Biobank of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (YBKB201909, YBKB202216); Joint Research Project of Institute of Biomaterials and Regenerative Medicine, Shanghai Jiao Tong University School of Medicine (2022LHB02).