Abstract：
:Recent studies have indicated that ATRA inhibits chondrogenesis and can lead to congenital clubfoot (CCF). The molecular mechanism of ATRA-induced chondrogenesis is not clear. As RhoA/ROCK and SDF-1/CXCR4 signaling play important molecular roles for a variety of cellular processes, we hypothesized that RhoA/ROCK2 and SDF-1/CXCR4 signaling are involved in ATRA-induced chondrogenesis in rat embryo hind limb bud mesenchymal cells (rEHBMCs). We found that ATRA dose-dependently inhibits proliferation and expression of chondrogenic transcription factors (SOX9 and COL2A1) in rEHBMCs. In contrast, ATRA increases the expression of ROCK2, SDF-1 and CXCR4. Pharmacological inhibition of ROCK signaling and SDF-1/CXCR4 signaling by Y27632 and AMD3100, respectively, resulted in elevated expression of SOX9 and COL2A1. In addition, we found that disturbing SDF-1/CXCR4 signaling by AMD3100 decreases ATRA-induced ROCK2 expression. In vivo studies we also confirm that SOX9 expression of early-stage cartilage progenitors in the proliferative zone and COL2A1 expression in prehypertrophic chondrocytes are decreased in ATRA-treated rat embryo hind limb. Together, these results show that ATRA activates SDF-1/CXCR4/ROCK2 signaling to inhibit chondrogenesis to lead to CCF by suppressing differentiation through down-regulation of SOX9 and COL2A1 expression in rat embryo hind limb bud mesenchymal cells.
journal_name
Am J Transl Resjournal_title
American journal of translational researchauthors
Hu QX,Li XD,Xie P,Wu CC,Zheng GZ,Lin FX,Xie D,Zhang QH,Liu DZ,Wang YG,Chang B,Du SXsubject
Has Abstractpub_date
2017-05-15 00:00:00pages
2296-2305issue
5issn
1943-8141journal_volume
9pub_type
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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更新日期：2015-08-15 00:00:00
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
pub_type： 杂志文章,评审
doi：
更新日期：2018-01-15 00:00:00
