image: (A) Construction of the Bmp9-KO mice. (B) Relative expression of Bmp9 in the liver of 8-week-old wild-type (WT) littermates and Bmp9-KO mice by quantitative PCR in vitro (n ≥ 3). (C) Western blots of BMP9 and β-actin in the liver of 8-week-old WT littermates and Bmp9-KO mice (n = 6). (D) Immunohistochemical staining of BMP9 on sections of mandibular first molars from WT littermates and Bmp9-KO mice at 2 weeks and 4 weeks old (n = 7). The boxes shown are insets at a lower magnification. Am, ameloblasts; Od, odontoblasts; D, dentin. (E) Quantitative analysis of BMP9 expression. Scale bars = 200 μm.
Credit: Chang Liu, Hongyan Yuan, Jindie Huang, Shidian Ran, Xiaorui Wei, Xingrui Yan, Linyu Xue, Tong-Chuan He, Yuxin Zhang, Mengqin Gu, Si Wu, Fugui Zhang, Wenping Luo, Hongmei Zhang
The interaction between Hertwig's epithelial root sheath (HERS) and surrounding mesenchymal cells is crucial for root dentin formation. HERS influences tooth root development and odontoblast differentiation; however, further research is needed to elucidate its regulatory mechanisms.
A new study published in the Genes & Diseases journal by researchers from the Affiliated Hospital of Stomatology of Chongqing Medical University, the Chongqing Municipal Health Commission Key Laboratory of Oral Biomedical Engineering, Southwest University, and the University of Chicago Medical Center provides mechanistic insights into how Bmp9 signaling impacts tooth root development.
The authors have previously shown that Bmp9 is crucial for tooth and alveolar bone formation, and in this study report that Bmp9 signaling modulates tooth root development by regulating the development of odontoblasts and HERS.
The authors generated Bmp9-KO mice and, upon comparison with their wild-type (WT) mice, observed that BMP9 plays a critical role in molar root development, dentin mineralization, and root elongation during early odontogenesis. Knockdown of Bmp9 inhibited odontoblast differentiation and also impacted the normal development of the mandibular first molars, as evidenced by shorter molar roots, wider apical foramen, and reduced dentin thickness. Bmp9 ablation disrupted odontoblast polarization, affecting their secretory capacity and weakening DSPP secretion, resulting in delayed dentin mineralization, increased collagen type I deposition, and reduced root length.
Furthermore, knockdown of Bmp9 inhibited cell proliferation within the HERS, thereby affecting HERS elongation and bending, and formation of the root apical foramen, which resulted in shorter roots, thinner dentin, and an unclosed apical foramen in Bmp9-KO mandibular first molars. Additional experiments involving Bmp9 overexpression and knockdown in primary HERS cells showed that “Bmp9 signaling modulates both HERS cell proliferation and intercellular junctions, thereby contributing to the proper development of tooth roots.”
Comparative transcriptomic profiling and pathway analysis (GO and KEGG) revealed that Bmp9 maintains HERS cell proliferation, junction homeostasis, and drives root morphogenesis by integrating a multidimensional regulatory network involving TGF-β and Wnt signaling and cell-cell connections.
In conclusion, this study is the first to report that BMP9 signaling influences root odontoblast function by regulating cell proliferation and intercellular junctions within HERS, thereby affecting the overall developmental trajectory of molar roots. The authors highlight the need for further research to identify specific binding sites and the mechanism of action of Bmp9 in regulating HERS proliferation and intercellular connectivity integrity.
Reference
Title of the original paper: Bmp9 modulates cell proliferation and intercellular junctions in HERS during tooth root development
Journal: Genes & Diseases
Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch
DOI: https://doi.org/10.1016/j.gendis.2025.101777
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