All-trans-retinoic acid suppresses rat embryo hindlimb bud mesenchymal chondrogenesis by modulating HoxD9 expression
| Autor: | Peng Xie, Shi-xin Du, Xue-dong Li, Quan Hong |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
animal structures
Mesenchyme Retinoic acid Tretinoin Bioengineering Hindlimb Applied Microbiology and Biotechnology chemistry.chemical_compound chondrogenesis GLI3 medicine Animals neoplasms Cells Cultured Homeodomain Proteins All-trans retinoic acid HoxD9 organic chemicals General Medicine Embryo Mammalian Chondrogenesis biological factors Neoplasm Proteins Rats Cell biology Blot Clubfoot medicine.anatomical_structure chemistry Apoptosis embryonic structures Signal transduction TP248.13-248.65 Research Article Research Paper club foot Biotechnology |
| Zdroj: | Bioengineered article-version (VoR) Version of Record Bioengineered, Vol 12, Iss 1, Pp 3900-3911 (2021) |
| ISSN: | 2165-5987 2165-5979 |
| Popis: | In vertebrates, 5ʹ-Hoxd genes (Hoxd9), which are expressed in the hindlimb bud mesenchyme, participate in limb growth and patterning in early embryonic development. In the present study, We investigated the mechanisms by which ATRA regulates cultured E12.5 rat embryo hindlimb bud mesenchymal cells (rEHBMCs). Following exposure to ATRA over 24 h, mRNA and protein expression levels of HoxD9 were evaluated by reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time PCR (qPCR), and western blotting. Flow cytometry was used to detect apoptosis. ATRA inhibited the condensation and proliferation, and promoted the apoptosis rate of the rEHBMCs in a dose-dependent manner. Sox9 and Col2a1 in rEHBMCs were downregulated by ATRA in a dose-dependent manner at both mRNA and protein levels. Similarly, HoxD9 was downregulated by ATRA in a dose-dependent manner, in parallel with the cartilage-specific molecules Sox9 and Col2a1. Both qPCR and western blotting showed that both Shh and Gli3 were downregulated. Overexpression of HoxD9 reversed the effects of ATRA. These results demonstrate that ATRA suppresses chondrogenesis in rEHBMCs by inhibiting the expression of HoxD9 and its downstream protein targets, including Sox9 and Col2a1. This effect may also be correlated with inhibition of the Shh-Gli3 signaling pathway. |
| Databáze: | OpenAIRE |
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