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miR‐193b‐5p regulates chondrocytes metabolism by directly targeting histone deacetylase 7 in interleukin‐1β‐induced osteoarthritis
Author(s) -
Zhang Chengyun,
Zhang Zhiqi,
Chang Zongkun,
Mao Guping,
Hu Shu,
Zeng Anyu,
Fu Ming
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28545
Subject(s) - microrna , cartilage , untranslated region , chemistry , luciferase , matrix metalloproteinase , mmp3 , downregulation and upregulation , osteoarthritis , endocrinology , gene expression , transfection , medicine , messenger rna , biochemistry , gene , anatomy , pathology , alternative medicine
There is increasing evidence regarding the pivotal roles of microRNAs (miRNAs) and histone deacetylases (HDACs) in the development of osteoarthritis (OA). This study aimed to determine whether miR‐193b‐5p regulates HDAC7 expression directly to affect cartilage degeneration. Expression levels of miR‐193b‐5p, HDAC7, matrix metalloproteinase 3 (MMP3), and MMP13 were determined in normal and OA cartilage and primary human chondrocytes (PHCs) stimulated with interleukin‐1β (IL‐1β). PHCs were transfected with a miR‐193b‐5p mimic or inhibitor to verify whether miR‐193b‐5p influences the expression of HDAC7 and MMPs. A luciferase reporter assay was performed to demonstrate the binding between miR‐193b‐5p and the 3′‐untranslated region (UTR) of HDAC7. Expression of miR‐193b‐5p was reduced in IL‐1β‐stimulated PHCs and in OA cartilage compared to that in normal cartilage. Luciferase reporter assay exhibited the repressed activity of the reporter construct containing the 3′UTR of HDAC7. Both miR‐193b‐5p overexpression and HDAC7 inhibition decreased the expression of MMP3 and MMP13, whereas the inhibition of miR‐193b‐5p enhanced HDAC7, MMP3, and MMP13 expression. miR‐193b‐5p downregulates HDAC7 directly and, as a result, inhibits MMP3 and MMP13 expression, which suggests that miR‐193b‐5p has a protective role in OA.