کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5508792 | 1400400 | 2016 | 35 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
MicroRNA-455-3p modulates cartilage development and degeneration through modification of histone H3 acetylation
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کلمات کلیدی
Sox9ITSTSARUNX2miR-455-3pHDACMIRPMCSCol2a1MMP13Small interfering RNA - RNA تداخل کوچکsiRNA - siRNAOsteoarthritis - استئوآرتریت(آرتروز)Histone acetylation - استیلیت هیستونTrichostatin A - تریکوستاتین ARunt-related transcription factor 2 - عامل رونویسی مرتبط با روت 2Matrix metalloproteinase 13 - ماتریکس متالوپروتئیناز 13MicroRNA - میکرو RNA Histone acetyltransferase - هیستون استیل ترانسفرازhistone deacetylase - هیستون داستیلازHAT - کلاهChondrogenesis - کندروژنیک
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Histone acetylation regulated by class I histone deacetylases (HDACs) plays a pivotal role in matrix-specific gene transcription and cartilage development. While we previously demonstrated that microRNA (miR)-455-3p is upregulated during chondrogenesis and can enhance early chondrogenesis, the mechanism underlying this process remains largely unclear. In this study, we characterized the effect of miR-455-3p on histone H3 acetylation and its role during cartilage development and degeneration. We observed that miR-455-3p was highly expressed in proliferating and pre-hypertrophic chondrocytes, while HDAC2 and HDAC8 were primarily expressed in hypertrophic chondrocytes. Meanwhile, miR-455-3p suppressed the activity of reporter constructs containing the 3â²-untranslated regions of HDAC2/8, inhibited HDAC2/8 expression and promoted histone H3 acetylation at the collagen 2 (COL2A1) promoter in human SW1353 chondrocyte-like cells. Treatment with the HDAC inhibitor trichostatin A (TSA) resulted in increased expression of cartilage-specific genes and promoted glycosaminoglycan deposition. Moreover, TSA inhibited matrix metalloproteinase 13 (Mmp13) expression and promoted nuclear translocation of SOX9 in interleukin-1-treated primary mouse chondrocytes. Lastly, knockdown of HDAC2/3/8 increased SRY (sex-determining region Y)-box 9 (SOX9) and decreased Runt-related transcription factor 2 (RUNX2) expression. Taken together, these findings suggest that miR-455-3p plays a critical role during chondrogenesis by directly targeting HDAC2/8 and promoting histone H3 acetylation, which raises possibilities of using miR-455-3p to influence chondrogenesis and cartilage degeneration.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1863, Issue 12, December 2016, Pages 2881-2891
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1863, Issue 12, December 2016, Pages 2881-2891
نویسندگان
Weishen M.D., Lingwu M.D., PHD, Ziji M.D., PHD, Fangang M.D., Guangxin M.D., Puyi M.D., PHD, Zhiqi M.D., PHD, Weiming M.D., PHD,