Distinctive role of ACVR1 in dentin formation: requirement for dentin thickness in molars and prevention of osteodentin formation in incisors of mice

Zhang, Xue; Shi, Ce; Zhao, Huan; Zhou, Yijun; Hu, Yue; Yan, Guangxing; Liu, Cangwei; Li, Daowei; Hao, Xinqing; Mishina, Yuji; Liu, Qilin; Sun, Hongchen

doi:10.1007/s10735-018-9806-z

Cited by 15 publications

(12 citation statements)

References 72 publications

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“…Loss of Acvr1 in the dental mesenchyme promoted dental defects. Additionally, Acvr1 was found to regulate dentin formation, odontoblast cell fate determination in incisors, and odontoblast differentiation in molars [87]. Altogether, these results highlight the essential role of ACVR1 as a regulator of osteogenic and chondrogenic differentiation and its importance in skeletal development.…”

Section: Bone Regulation and Skeletal Developmentmentioning

confidence: 99%

ACVR1 Function in Health and Disease

Valer

Sánchez-de-Diego

Pimenta-Lopes

et al. 2019

Cells

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Activin A receptor type I (ACVR1) encodes for a bone morphogenetic protein type I receptor of the TGFβ receptor superfamily. It is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation. Moreover, ACVR1 has been extensively studied for its causal role in fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder characterised by progressive heterotopic ossification. ACVR1 is linked to different pathologies, including cardiac malformations and alterations in the reproductive system. More recently, ACVR1 has been experimentally validated as a cancer driver gene in diffuse intrinsic pontine glioma (DIPG), a malignant childhood brainstem glioma, and its function is being studied in other cancer types. Here, we review ACVR1 receptor function and signalling in physiological and pathological processes and its regulation according to cell type and mutational status. Learning from different functions and alterations linked to ACVR1 is a key step in the development of interdisciplinary research towards the identification of novel treatments for these pathologies.

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Section: Bone Regulation and Skeletal Developmentmentioning

confidence: 99%

ACVR1 Function in Health and Disease

Valer

Sánchez-de-Diego

Pimenta-Lopes

et al. 2019

Cells

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“…All these indicated that activation and up-regulated expression of ACVR1 possibly played a very important role in the proliferation and anti-apoptosis process of intestinal epithelial cells with Hp, as for the mechanism activating ACVR1 by Hp infection, some studies reported that the relative antigen CagA of cytotoxin could up-regulate the expression of ACVR1. [16][17][18] Bcl-2 family is the gene family regulating the cell apoptosis on which the most attention is paid, including Bcl-2 and Bcl-XL, which as the earliest apoptotic inhibitors are one of the inducible apoptotic inhibitors of ACVR1. 14 Studies find out that the activation of ACVR1 could enhance the expression of anti-apoptotic genes in the Bcl-2 family, thus having the anti-apoptosis effect.…”

Section: Discussionmentioning

confidence: 99%

Influence on proliferation and apoptosis of intestinal epithelial cells and expression of ACVR1 by Helicobacter pylori

et al. 2021

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To discuss the influence on proliferation and apoptosis of human intestinal epithelial cells by Helicobacter pylori (Hp). CCK-8 method and flow cytometry to test the influence on proliferation and apoptosis of intestinal epithelial cells by Hp and cell cycle distribution. Immunocytochemistry, qRT-PCR, and WB to analyze the expression and activation of ACVR1. Functional studies of TNBS-induced IBD on mice and DSS-induced IBD on C57BL/6J mice with HP used for intervention were also performed. Hp facilitated the proliferation of intestinal epithelial cells with the breeding ratios on the first and third day are 5.24% ± 3.26% and 34.18% ± 6.68% respectively. ACVR1 is activated and the expression of anti-apoptosis protein Bcl-2 and Bcl-XL is up-regulated. In vivo, TNBS-induced and Hp-induced exhibited inflammatory lesions of intestine, ACVR1 and Bcl-2 higher expressions as compared to wild-type mice. Hp is likely to play a very important role in the proliferation, apoptosis, and malignant transformation of intestinal epithelial cells through ACVR1 pathway.

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“…Interestingly, BMP‐2 deletion in odontoblasts results in osteodentin formation in molar roots . The deletion of AcvR1, another BMP type 1 receptor, results in osteodentin formation in the incisor but not in the molar, suggesting that loss of BMP signaling alters odontoblast phenotype in a site‐specific manner. Here, however, we did not observe osteodentin in the Bmpr1a cKO molars during primary dentin formation.…”

Section: Discussionmentioning

confidence: 99%

BMP‐Smad Signaling Regulates Postnatal Crown Dentinogenesis in Mouse Molar

et al. 2019

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Dentinogenesis, a formation of dentin by odontoblasts, is an essential process during tooth development. Bone morphogenetic proteins (BMPs) are one of the most crucial growth factors that contribute to dentin formation. However, it is still unclear how BMP signaling pathways regulate postnatal crown and root dentinogenesis. BMPs transduce signals through canonical Smad and non‐Smad signaling pathways including p38 and ERK signaling pathways. To investigate the roles of Smad and non‐Smad signaling pathways in dentinogenesis, we conditionally deleted Bmpr1a, which encodes the type 1A receptor for BMPs, to remove both Smad and non‐Smad pathways in Osterix‐expressing cells. We also expressed a constitutively activated form of Bmpr1a (caBmpr1a) to increase Smad1/5/9 signaling activity without altered non‐Smad activity in odontoblasts. To understand the function of BMP signaling during postnatal dentin formation, Cre activity was induced at the day of birth. Our results showed that loss of BmpR1A in odontoblasts resulted in impaired dentin formation and short molar roots at postnatal day 21. Bmpr1a cKO mice displayed a reduction of dentin matrix production compared to controls associated with increased cell proliferation and reduced Osx and Dspp expression. In contrast, caBmpr1a mutant mice that show increased Smad1/5/9 signaling activity resulted in no overt tooth phenotype. To further dissect the functions of each signaling activity, we generated Bmpr1a cKO mice also expressing caBmpr1a to restore only Smad1/5/9 signaling activity. Restoring Smad activity in the compound mutant mice rescued impaired crown dentin formation in the Bmpr1a cKO mice; however, impaired root dentin formation and short roots were not changed. These results suggest that BMP‐Smad signaling in odontoblasts is responsible for crown dentin formation, while non‐Smad signaling may play a major role in root dentin formation and elongation. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Distinctive role of ACVR1 in dentin formation: requirement for dentin thickness in molars and prevention of osteodentin formation in incisors of mice

Cited by 15 publications

References 72 publications

ACVR1 Function in Health and Disease

ACVR1 Function in Health and Disease

Influence on proliferation and apoptosis of intestinal epithelial cells and expression of ACVR1 by Helicobacter pylori

BMP‐Smad Signaling Regulates Postnatal Crown Dentinogenesis in Mouse Molar

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