All-trans-retinoid acid (ATRA) suppresses chondrogenesis of rat primary hind limb bud mesenchymal cells by downregulating p63 and cartilage-specific molecules

Wang, Yunguo; Xie, Peng; Wang, Yungong; Li, Xuedong; Zhang, Tao-gen; Liu, Zhao-yong; Hong, Quan; Du, Shasha

doi:10.1016/j.etap.2014.07.008

Cited by 6 publications

(12 citation statements)

References 42 publications

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“…Interestingly, the osteogenic differentiation of MEPM cells from atRA-induced cleft palates were also weaker than MEPM cells from normal palates. We did not determine whether atRA could affect adipogenic and chondrogenic differentiation, but there are many other studies that show that atRA could block adipogenic differentiation by MEPM cells [73][74][75] and chondrogenic differentiation [76][77][78][79][80] . Our results showed that atRA regulated osteogenic differentiation through the disruption of MEPM cell stemness and pluripotency.…”

Section: Discussionmentioning

confidence: 99%

All-trans Retinoic Acid Regulates miR-106a-5p Inhibition of Autophagic in Developing Cleft Palates

Shi

Liang

Liu

et al. 2020

Preprint

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All-trans retinoic acid (atRA) results in cleft palate, but the cellular and molecular mechanisms underlying the teratogenic effects on palatal development have not been fully elucidated. Autophagy interruption has been reported to seriously affect embryonic-cell differentiation and development. This study aimed to verify whether atRA-induced cleft palate occurs because atRA blocks autophagy and stemness of embryonic palatal mesenchyme (MEPM) cells, which are maintained via the phosphatase and tensin homolog (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) autophagic signaling pathway, and inhibits osteogenic-differentiation potential of MEPM cells, which could lead to the development of cleft palate.

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Section: Discussionmentioning

confidence: 99%

All-trans Retinoic Acid Regulates miR-106a-5p Inhibition of Autophagic in Developing Cleft Palates

Shi

Liang

Liu

et al. 2020

Preprint

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“…Mutations affecting the expression of TRP63 are associated with a wide spectrum of limb phenotypes: While the knockout of Trp63 results in severe truncation of both limbs, knock-in of an SHFM mutation Arg279His causes a complete reduction of hindlimbs and milder reduction of forelimbs (Yang et al 1999;Vanbokhoven et al 2011). In contrast, treatment of mice with retinoic acid was shown to cause lower limb duplications, polydactyly, and oligodactyly, at least in part due to downregulation of Trp63 (Niederreither et al 1996;Wang et al 2014b). Therefore we speculate that mutations in ZAK causing a down-regulation of Trp63 in the hindlimb give rise to a wide spectrum of lower limb phenotypes with reduced penetrance and variable expressivity.…”

Section: Discussionmentioning

confidence: 99%

“…We noted that the mutant mice looked similar to mice treated in utero with retinoic acid, showing lower limb duplications and hindlimb oligodactyly (Niederreither et al 1996). Treatment of limb bud cells with retinoic acid results in a downregulation of Trp63 (Wang et al 2014b). We therefore performed quantitative reverse transcription-PCR (qRT-PCR) for Trp63 in Zak-mutant limb tissue (Yang et al 2006) and detected a 60% decrease of Trp63 expression in homozygous versus wild-type hindlimbs (Fig.…”

Section: Generation and Analysis Of Zakmentioning

confidence: 99%

Exome sequencing and CRISPR/Cas genome editing identify mutations of ZAK as a cause of limb defects in humans and mice

et al. 2016

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The CRISPR/Cas technology enables targeted genome editing and the rapid generation of transgenic animal models for the study of human genetic disorders. Here we describe an autosomal recessive human disease in two unrelated families characterized by a split-foot defect, nail abnormalities of the hands, and hearing loss, due to mutations disrupting the SAM domain of the protein kinase ZAK. ZAK is a member of the MAPKKK family with no known role in limb development. We show that Zak is expressed in the developing limbs and that a CRISPR/Cas-mediated knockout of the two Zak isoforms is embryonically lethal in mice. In contrast, a deletion of the SAM domain induces a complex hindlimb defect associated with down-regulation of Trp63, a known split-hand/split-foot malformation disease gene. Our results identify ZAK as a key player in mammalian limb patterning and demonstrate the rapid utility of CRISPR/Cas genome editing to assign causality to human mutations in the mouse in <10 wk.

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“…An in vitro study showed that a heparanase antagonist SST0001 successfully inhibited chondrogenesis. It suggests that further investigation may be profitable chondrogenesis (Wang et al, 2014;Inubushi et al, 2018) Other potential and promising treatment targets are presented in Table 3. They include BMP and Hedgehog signaling pathways or an enzyme heparanase (Yoon et al, 2006;Bovée et al, 2010;Heuzé et al, 2014;Huegel et al, 2015;Mundy et al, 2016;Sinha et al, 2017;Inubushi et al, 2018;Pacifici, 2018).…”

Section: Heparanasementioning

confidence: 99%

Hereditary Multiple Exostoses—A Review of the Molecular Background, Diagnostics, and Potential Therapeutic Strategies

et al. 2021

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Hereditary multiple exostoses (HMEs) syndrome, also known as multiple osteochondromas, represents a rare and severe human skeletal disorder. The disease is characterized by multiple benign cartilage-capped bony outgrowths, termed exostoses or osteochondromas, that locate most commonly in the juxta-epiphyseal portions of long bones. Affected individuals usually complain of persistent pain caused by the pressure on neighboring tissues, disturbance of blood circulation, or rarely by spinal cord compression. However, the most severe complication of this condition is malignant transformation into chondrosarcoma, occurring in up to 3.9% of HMEs patients. The disease results mainly from heterozygous loss-of-function alterations in the EXT1 or EXT2 genes, encoding Golgi-associated glycosyltransferases, responsible for heparan sulfate biosynthesis. Some of the patients with HMEs do not carry pathogenic variants in those genes, hence the presence of somatic mutations, deep intronic variants, or another genes/loci is suggested. This review presents the systematic analysis of current cellular and molecular concepts of HMEs along with clinical characteristics, clinical and molecular diagnostic methods, differential diagnosis, and potential treatment options.

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All-trans-retinoid acid (ATRA) suppresses chondrogenesis of rat primary hind limb bud mesenchymal cells by downregulating p63 and cartilage-specific molecules

Cited by 6 publications

References 42 publications

All-trans Retinoic Acid Regulates miR-106a-5p Inhibition of Autophagic in Developing Cleft Palates

All-trans Retinoic Acid Regulates miR-106a-5p Inhibition of Autophagic in Developing Cleft Palates

Exome sequencing and CRISPR/Cas genome editing identify mutations of ZAK as a cause of limb defects in humans and mice

Hereditary Multiple Exostoses—A Review of the Molecular Background, Diagnostics, and Potential Therapeutic Strategies

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