Retinoic acid retards fetal and hindlimb skeletal development asymmetrically in a retinoic acid-induced clubfoot model

Liu, Zhao-Yong; Li, Xuedong; Chen, Bin; Zheng, Cuifang; Zhong, Yongsheng; Jia, Yanli; Du, Shasha

doi:10.1016/j.etp.2010.05.003

Cited by 4 publications

(3 citation statements)

References 17 publications

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“…Additionally, it has been proposed that the teratogenic effects of ATRA, leading to limb defects, are based on increased cellular apoptosis in the developing limb ( 33 , 34 ). Previous studies by our group have demonstrated that a rat embryo CCF-like model may be established via a single intragastric dose of ATRA, which exhibits hindlimb congenital malformations, impaired chondrogenesis and increased cellular apoptosis ( 3 , 4 , 35 ). These findings suggested that defective chondrogenesis of the primary hindlimb bud mesenchymal cells may contribute to CCF.…”

Section: Discussionmentioning

confidence: 99%

“…Delgado-Baeza et al ( 2 ) have established a fetal rat clubfoot model using a single intragastric dose of RA on day 10 of gestation. Our group previously demonstrated that inhibition of hindlimb cartilage development is a crucial factor for ATRA-induced congenital clubfoot (CCF) in a rat model ( 3 , 4 ). Limb patterning and growth are carefully regulated through a complex network of transcription factors and signaling molecules ( 5 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

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All-trans-retinoic acid inhibits chondrogenesis of rat embryo hindlimb bud mesenchymal cells by downregulating p53 expression

Zhang

et al. 2015

Molecular Medicine Reports

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Despite the well-established role of all-trans-retinoic acid (ATRA) in congenital clubfoot (CCF)-like deformities in in vivo models, the essential cellular and molecular targets and the signaling mechanisms for ATRA-induced CCF-like deformities remain to be elucidated. Recent studies have demonstrated that p53 and p21, expressed in the hindlimb bud mesenchyme, regulate cellular proliferation and differentiation, contributing to a significant proportion of embryonic CCF-like abnormalities. The objective of the present study was to investigate the mechanisms for ATRA-induced CCF, by assessing ATRA-regulated chondrogenesis in rat embryo hindlimb bud mesenchymal cells (rEHBMCs) in vitro. The experimental study was based on varying concentrations of ATRA exposure on embryonic day 12.5 rEHBMCs in vitro. The present study demonstrated that ATRA inhibited the proliferation of cells by stimulating apoptotic cell death of rEHBMCs. It was also observed that ATRA induced a dose-dependent reduction of cartilage nodules compared with the control group. Reverse transcription-polymerase chain reaction and western blotting assays revealed that the mRNA and protein expression of cartilage-specific molecules, including aggrecan, Sox9 and collagen, type II, α 1 (Col2a1), were downregulated by ATRA in a dose-dependent manner; the mRNA levels of p53 and p21 were dose-dependently upregulated from 16 to 20 h of incubation with ATRA, but dose-dependently downregulated from 24 to 48 h. Of note, p53 and p21 were regulated at the translational level in parallel with the transcription with rEHBMCs treated with ATRA. Furthermore, the immunofluorescent microscopy assays indicated that proteins of p53 and p21 were predominantly expressed in the cartilage nodules. The present study demonstrated that ATRA decreases the chondrogenesis of rEHBMCs by inhibiting cartilage-specific molecules, including aggrecan, Sox9 and Col2al, via regulating the expression of p53 and p21.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

All-trans-retinoic acid inhibits chondrogenesis of rat embryo hindlimb bud mesenchymal cells by downregulating p53 expression

Zhang

et al. 2015

Molecular Medicine Reports

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“…Z-Y Liu y cols. comprobaron la pobre osificación de los metatarsianos, la ausencia de falanges distales y la ausencia de los centros de osificación en fémur, tibia y peroné en un modelo animal experimental tras la administración de ácido retinoico (13).…”

Section: Introductionunclassified

Eficacia del método Ponseti en el tratamiento del pie equinovaro

Morales

2019

Rev. Int. Cienc. Podol.

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Contexto: El pie equinovaro es una deformidad musculoesquelética congénita caracterizada por la presencia de cavo, varo, adducto y equino. Afecta a 1-7 de cada 1000 nacimientos. Un pie zambo no tratado puede generar dolor y discapacidad durante la vida de la persona. El método Ponseti se ha convertido en la principal modalidad de tratamiento para el manejo del pie zambo produciendo buenos resultados a largo plazo. El objetivo de este manuscrito fue evaluar la eficacia del método Ponseti y la evolución de los pacientes en función de las tasas de recurrencia, tenotomías y cirugías asociadas. También se determinó si la edad de los niños influía en el éxito del tratamiento. Métodos: Se realizó una estrategia de búsqueda a través de Pubmed hasta abril de 2018. Los términos de búsqueda incluyeron pie zambo, método Ponseti y pie equinovaro. Se incluyeron metaanálisis, revisiones sistemáticas, ensayos clínicos y series de casos. También se examinaron las referencias bibliográficas de los artículos seleccionados. Resultados: Veintisiete artículos fueron incluidos en esta revisión. La literatura actual muestra una tasa de éxito del 78-92% utilizando el método Ponseti. Conclusión: El método Ponseti ofrece resultados alentadores en términos funcionales y estéticos, así como disminución del grado de corrección quirúrgica cuando los resultados no sean los esperados. Se necesita más investigación para generar evidencia de mayor calidad con mayores tamaños muestrales y unificación a la hora de medir la severidad de la deformidad. Otra limitación encontrada fue la ausencia de la definición de fracaso de tratamiento y sus correspondientes motivos.

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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

Wang¹,

Xie²,

Wang³

et al. 2014

Environmental Toxicology and Pharmacology

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Retinoic acid retards fetal and hindlimb skeletal development asymmetrically in a retinoic acid-induced clubfoot model

Cited by 4 publications

References 17 publications

All-trans-retinoic acid inhibits chondrogenesis of rat embryo hindlimb bud mesenchymal cells by downregulating p53 expression

All-trans-retinoic acid inhibits chondrogenesis of rat embryo hindlimb bud mesenchymal cells by downregulating p53 expression

Eficacia del método Ponseti en el tratamiento del pie equinovaro

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

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