scholarly journals Epithelial Bone Morphogenic Protein 2 and 4 Are Indispensable for Tooth Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Haibin Mu ◽  
Xin Liu ◽  
Shuoshuo Geng ◽  
Dian Su ◽  
Heran Chang ◽  
...  
Keyword(s):  
Cell Death ◽  
Cellular Differentiation ◽  
Tooth Development ◽  
Erk Signaling ◽  
Tooth Root ◽  
Short Root ◽  
Root Sheath ◽  
Bone Morphogenic Protein 2 ◽  
Low Dosage

The Bmp2 and Bmp4 expressed in root mesenchyme were essential for the patterning and cellular differentiation of tooth root. The role of the epithelium-derived Bmps in tooth root development, however, had not been reported. In this study, we found that the double abrogation of Bmp2 and Bmp4 from mouse epithelium caused short root anomaly (SRA). The K14-cre;Bmp2f/f;Bmp4f/f mice exhibited a persistent Hertwig’s Epithelial Root Sheath (HERS) with the reduced cell death, and the down-regulated BMP-Smad4 and Erk signaling pathways. Moreover, the Shh expression in the HERS, the Shh-Gli1 signaling, and Nfic expression in the root mesenchyme of the K14-cre;Bmp2f/f;Bmp4f/f mice were also decreased, indicating a disrupted epithelium- mesenchyme interaction between HERS and root mesenchyme. Such disruption suppressed the Osx and Dspp expression in the root mesenchyme, indicating an impairment on the differentiation and maturation of root odontoblasts. The impaired differentiation and maturation of root odontoblasts could be rescued partially by transgenic Dspp. Therefore, although required in a low dosage and with a functional redundancy, the epithelial Bmp2 and Bmp4 were indispensable for the HERS degeneration, as well as the differentiation and maturation of root mesenchyme.

scholarly journals Signaling Pathways Critical for Tooth Root Formation

2017 ◽  
Vol 96 (11) ◽  
pp. 1221-1228 ◽  
Author(s):  
J. Wang ◽  
J.Q. Feng
Keyword(s):  
Signaling Pathways ◽  
Root Formation ◽  
Root Resorption ◽  
Tooth Development ◽  
Critical Role ◽  
Future Research ◽  
Tooth Root ◽  
Short Root ◽  
Dentin Formation

Tooth is made of an enamel-covered crown and a cementum-covered root. Studies on crown dentin formation have been a major focus in tooth development for several decades. Interestingly, the population prevalence for genetic short root anomaly (SRA) with no apparent defects in crown is close to 1.3%. Furthermore, people with SRA itself are predisposed to root resorption during orthodontic treatment. The discovery of the unique role of Nfic (nuclear factor I C; a transcriptional factor) in controlling root but not crown dentin formation points to a new concept: tooth crown and root have different control mechanisms. Further genetic mechanism studies have identified more key molecules (including Osterix, β-catenin, and sonic hedgehog) that play a critical role in root formation. Extensive studies have also revealed the critical role of Hertwig’s epithelial root sheath in tooth root formation. In addition, Wnt10a has recently been found to be linked to multirooted tooth furcation formation. These exciting findings not only fill the critical gaps in our understanding about tooth root formation but will aid future research regarding the identifying factors controlling tooth root size and the generation of a whole “bio-tooth” for therapeutic purposes. This review starts with human SRA and mainly focuses on recent progress on the roles of NFIC-dependent and NFIC-independent signaling pathways in tooth root formation. Finally, this review includes a list of the various Cre transgenic mouse lines used to achieve tooth root formation–related gene deletion or overexpression, as well as strengths and limitations of each line.

scholarly journals USP34 regulates tooth root morphogenesis by stabilizing NFIC

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Shuang Jiang ◽  
Rui Sheng ◽  
Xingying Qi ◽  
Jun Wang ◽  
Yuchen Guo ◽  
...  
Keyword(s):  
Tooth Development ◽  
Tooth Root ◽  
Short Root ◽  
Physiological Processes ◽  
Root Sheath ◽  
Specific Protease ◽  
Nuclear Factor I ◽  
Root Morphogenesis ◽  
Dependent Protein ◽  
Pulp Cells

AbstractTooth root morphogenesis involves two biological processes, root elongation and dentinogenesis, which are guaranteed by downgrowth of Hertwig’s epithelial root sheath (HERS) and normal odontoblast differentiation. Ubiquitin-dependent protein degradation has been reported to precisely regulate various physiological processes, while its role in tooth development is still elusive. Here we show ubiquitin-specific protease 34 (USP34) plays a pivotal role in root formation. Deletion of Usp34 in dental mesenchymal cells leads to short root anomaly, characterized by truncated roots and thin root dentin. The USP34-deficient dental pulp cells (DPCs) exhibit decreased odontogenic differentiation with downregulation of nuclear factor I/C (NFIC). Overexpression of NFIC partially restores the impaired odontogenic potential of DPCs. These findings indicate that USP34-dependent deubiquitination is critical for root morphogenesis by stabilizing NFIC.

scholarly journals The Impact of the Eda Pathway on Tooth Root Development

2017 ◽  
Vol 96 (11) ◽  
pp. 1290-1297 ◽  
Author(s):  
J.M. Fons Romero ◽  
H. Star ◽  
R. Lav ◽  
S. Watkins ◽  
M. Harrison ◽  
...  
Keyword(s):  
Root Development ◽  
Tooth Development ◽  
Mouse Development ◽  
Direct Role ◽  
Root Sheath ◽  
Crown Shape ◽  
High Incidence ◽  
Tooth Number ◽  
The Impact

The Eda pathway ( Eda, Edar, Edaradd) plays an important role in tooth development, determining tooth number, crown shape, and enamel formation. Here we show that the Eda pathway also plays a key role in root development. Edar (the receptor) is expressed in Hertwig’s epithelial root sheath (HERS) during root development, with mutant mice showing a high incidence of taurodontism: large pulp chambers lacking or showing delayed bifurcation or trifurcation of the roots. The mouse upper second molars in the Eda pathway mutants show the highest incidence of taurodontism, this enhanced susceptibility being matched in human patients with mutations in EDA-A1. These taurodont teeth form due to defects in the direction of extension of the HERS from the crown, associated with a more extensive area of proliferation of the neighboring root mesenchyme. In those teeth where the angle at which the HERS extends from the crown is very wide and therefore more vertical, the mutant HERSs fail to reach toward the center of the tooth in the normal furcation region, and taurodont teeth are created. The phenotype is variable, however, with milder changes in angle and proliferation leading to normal or delayed furcation. This is the first analysis of the role of Eda in the root, showing a direct role for this pathway during postnatal mouse development, and it suggests that changes in proliferation and angle of HERS may underlie taurodontism in a range of syndromes.

Role of Hertwig's epithelial root sheath cells in tooth root development

2003 ◽  
Vol 228 (4) ◽  
pp. 651-663 ◽  
Author(s):  
Margarita Zeichner-David ◽  
Keiji Oishi ◽  
Zhengyan Su ◽  
Vassili Zakartchenko ◽  
Li-Sha Chen ◽  
...  
Keyword(s):  
Root Development ◽  
Tooth Root ◽  
Hertwig’S Epithelial Root Sheath ◽  
Root Sheath ◽  
Sheath Cells

The role of programmed cell death ligand-1/ programmed cell death-1 (PD-L1/PD-1) in HPV-induced cervical cancer and potential for their use in blockade therapy

2020 ◽  
Vol 27 ◽  
Author(s):  
Lifang Zhang ◽  
Yu Zhao ◽  
Quanmei Tu ◽  
Xiangyang Xue ◽  
Xueqiong Zhu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Escape ◽  
Hypoxia Inducible Factor ◽  
Hpv Infection ◽  
Advanced Cervical Cancer ◽  
Cervical Carcinogenesis ◽  
Programmed Cell Death 1

Background: Cervical cancer induced by infection with human papillomavirus (HPV) remains a leading cause of mortality for women worldwide although preventive vaccines and early diagnosis have reduced morbidity and mortality. Advanced cervical cancer can only be treated with either chemotherapy or radiotherapy but outcomes are poor. The median survival for advanced cervical cancer patients is only 16.8 months. Methods: We undertook a structural search of peer-reviewed published studies based on 1). Characteristics of programmed cell death ligand-1/programmed cell death-1(PD-L1/PD-1) expression in cervical cancer and upstream regulatory signals of PD-L1/PD-1 expression, 2). The role of the PD-L1/PD-1 axis in cervical carcinogenesis induced by HPV infection and 3). Whether the PD-L1/PD-1 axis has emerged as a potential target for cervical cancer therapies. Results: One hundred and twenty-six published papers were included in the review, demonstrating that expression of PD-L1/PD-1 is associated with HPV-caused cancer, especially with HPV 16 and 18 which account for approximately 70% of cervical cancer cases. HPV E5/E6/E7 oncogenes activate multiple signaling pathways including PI3K/AKT, MAPK, hypoxia-inducible factor 1α, STAT3/NF-kB and MicroRNAs, which regulate PD-L1/PD-1 axis to promote HPV-induced cervical carcinogenesis. The PD-L1/PD-1 axis plays a crucial role in immune escape of cervical cancer through inhibition of host immune response. creating an "immune-privileged" site for initial viral infection and subsequent adaptive immune resistance, which provides a rationale for therapeutic blockade of this axis in HPV-positive cancers. Currently, Phase I/II clinical trials evaluating the effects of PD-L1/PD-1 targeted therapies are in progress for cervical carcinoma, which provide an important opportunity for the application of anti-PD-L1/anti-PD-1 antibodies in cervical cancer treatment. Conclusion: Recent research developments have led to an entirely new class of drugs using antibodies against the PD-L1/PD-1 thus promoting the body’s immune system to fight the cancer. The expression and roles of the PD-L1/ PD-1 axis in the progression of cervical cancer provide great potential for using PD-L1/PD-1 antibodies as a targeted cancer therapy.

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