<i>Rmrp</i> Mutation Disrupts Chondrogenesis and Bone Ossification in Zebrafish Model of Cartilage-Hair Hypoplasia via Enhanced Wnt/β-Catenin Signaling

Sun, Xianding; Zhang, Ruobin; Liu, Mi; Chen, Hangang; Chen, Liang; Luo, Fei; Zhang, Dali; Huang, Junlan; Li, Fangfang; Ni, Zhenhong; Qi, Han; Su, Nan; Jin, Min; Yang, Jing; Tan, Qiaoyan; Du, Xiaolan; Chen, Bin; Huang, Haiyang; Chen, Shuai; Liang, Yin; Xu, Xiaoling; Deng, Chu‐Xia; Luo, Lingfei; Xie, Yangli; Chen, Lin

doi:10.1002/jbmr.3820

Cited by 17 publications

(13 citation statements)

References 52 publications

(110 reference statements)

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“…Targeting a conserved region of rmrp in zebrafish and reducing its level led to some CHH phenotypes, as well as to decreased cell proliferation, increased apoptosis, and increased lethality 12-14 d after fertilization. The effect of rmrp deficiency was attributed to increased Wnt/β-catenin signaling, as inhibition of Wnt/β-catenin partially alleviated the phenotype of rmrp deficit (Sun et al 2019).…”

Section: Rmrp and Cartilage Hair Hypoplasiamentioning

confidence: 99%

RNA polymerase III transcription as a disease factor

Yeganeh

Hernandez

2020

Genes Dev.

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RNA polymerase (Pol) III is responsible for transcription of different noncoding genes in eukaryotic cells, whose RNA products have well-defined functions in translation and other biological processes for some, and functions that remain to be defined for others. For all of them, however, new functions are being described. For example, Pol III products have been reported to regulate certain proteins such as protein kinase R (PKR) by direct association, to constitute the source of very short RNAs with regulatory roles in gene expression, or to control microRNA levels by sequestration. Consistent with these many functions, deregulation of Pol III transcribed genes is associated with a large variety of human disorders. Here we review different human diseases that have been linked to defects in the Pol III transcription apparatus or to Pol III products imbalance and discuss the possible underlying mechanisms.

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Section: Rmrp and Cartilage Hair Hypoplasiamentioning

confidence: 99%

RNA polymerase III transcription as a disease factor

Yeganeh

Hernandez

2020

Genes Dev.

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“…RMRP mutations have been associated with inhibition of intramembranous ossification of skull bones and activation of vertebrae ossification. Moreover, disrupted RMRP inhibits cell proliferation, promotes apoptosis and activates the Wnt/β-catenin pathway, probably by suppressing the degradation of β-catenin [ 92 ].…”

Section: Ribosomopathies With Specific Correctionsmentioning

confidence: 99%

Ribosomopathies: New Therapeutic Perspectives

Orgebin

Lamoureux

Isidor

et al. 2020

Cells

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Ribosomopathies are a group of rare diseases in which genetic mutations cause defects in either ribosome biogenesis or function, given specific phenotypes. Ribosomal proteins, and multiple other factors that are necessary for ribosome biogenesis (rRNA processing, assembly of subunits, export to cytoplasm), can be affected in ribosomopathies. Despite the need for ribosomes in all cell types, these diseases result mainly in tissue-specific impairments. Depending on the type of ribosomopathy and its pathogenicity, there are many potential therapeutic targets. The present manuscript will review our knowledge of ribosomopathies, discuss current treatments, and introduce the new therapeutic perspectives based on recent research. Diamond–Blackfan anemia, currently treated with blood transfusion prior to steroids, could be managed with a range of new compounds, acting mainly on anemia, such as L-leucine. Treacher Collins syndrome could be managed by various treatments, but it has recently been shown that proteasomal inhibition by MG132 or Bortezomib may improve cranial skeleton malformations. Developmental defects resulting from ribosomopathies could be also treated pharmacologically after birth. It might thus be possible to treat certain ribosomopathies without using multiple treatments such as surgery and transplants. Ribosomopathies remain an open field in the search for new therapeutic approaches based on our recent understanding of the role of ribosomes and progress in gene therapy for curing genetic disorders.

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“…The Tg (sp7:EGFP) b 1212 line allowed osteoblast behavior to be studied during both intramembranous and endochondral ossification. Moreover, this line was used to investigate the abnormal perichondral ossification in the RNA component of the mitochondrial RNA-processing endoribonuclease ( rmrp ) knock-out zebrafish model of cartilage hair hypoplasia ( 65 ). Tg(Ola.sp7 : mCherry) zf 131 was crossed with the OI type XIII zebrafish model frilly fins to elucidate the role of the bone morphogenic protein 1, encoded by bmp1a gene, in osteoblast differentiation and localization ( 94 ).…”

Section: Transgenic Linesmentioning

confidence: 99%

Zebrafish: A Resourceful Vertebrate Model to Investigate Skeletal Disorders

et al. 2020

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Animal models are essential tools for addressing fundamental scientific questions about skeletal diseases and for the development of new therapeutic approaches. Traditionally, mice have been the most common model organism in biomedical research, but their use is hampered by several limitations including complex generation, demanding investigation of early developmental stages, regulatory restrictions on breeding, and high maintenance cost. The zebrafish has been used as an efficient alternative vertebrate model for the study of human skeletal diseases, thanks to its easy genetic manipulation, high fecundity, external fertilization, transparency of rapidly developing embryos, and low maintenance cost. Furthermore, zebrafish share similar skeletal cells and ossification types with mammals. In the last decades, the use of both forward and new reverse genetics techniques has resulted in the generation of many mutant lines carrying skeletal phenotypes associated with human diseases. In addition, transgenic lines expressing fluorescent proteins under bone cell-or pathway-specific promoters enable in vivo imaging of differentiation and signaling at the cellular level. Despite the small size of the zebrafish, many traditional techniques for skeletal phenotyping, such as x-ray and microCT imaging and histological approaches, can be applied using the appropriate equipment and custom protocols. The ability of adult zebrafish to remodel skeletal tissues can be exploited as a unique tool to investigate bone formation and repair. Finally, the permeability of embryos to chemicals dissolved in water, together with the availability of large numbers of small-sized animals makes zebrafish a perfect model for high-throughput bone anabolic drug screening. This review aims to discuss the techniques that make zebrafish a powerful model to investigate the molecular and physiological basis of skeletal disorders.

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Rmrp Mutation Disrupts Chondrogenesis and Bone Ossification in Zebrafish Model of Cartilage-Hair Hypoplasia via Enhanced Wnt/β-Catenin Signaling

Cited by 17 publications

References 52 publications

RNA polymerase III transcription as a disease factor

RNA polymerase III transcription as a disease factor

Ribosomopathies: New Therapeutic Perspectives

Zebrafish: A Resourceful Vertebrate Model to Investigate Skeletal Disorders

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