MicroRNA-92a Upholds Bmp Signaling by Targeting noggin3 during Pharyngeal Cartilage Formation

Guan, Ning; Liu, Xiuli; Dai, Miaomiao; Meng, Anming; Wang, Qiang

doi:10.1016/j.devcel.2012.12.016

Cited by 79 publications

(88 citation statements)

References 73 publications

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“…Ning et al [40] demonstrated a positive effect of miR-92a on the proliferation, differentiation, and survival of chondrogenic progenitor cells by targeting nog3, an inhibitor of the BMP signaling pathway. MiR-92a expression decreases rapidly in macrophages upon stimulation with Toll-like receptor ligands, and miR-92a controls the inflammatory response by targeting the MKK4/JNK/c-Jun pathway [41].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes

Mao¹,

Zhang²,

Zhang³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5) are secreted enzymes belonging to the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family that play significant roles in the progression of osteoarthritis (OA). Here, we aimed to determine whether the expression of ADAMTS-4/5 in chondrogenesis and inflammation is regulated by microRNA-92a-3p (miR-92a-3p). Methods: MiR-92a-3p and ADAMTS-4/5 expressions were determined by quantitative polymerase chain reaction (qPCR). To investigate the repressive effect of miR-92a-3p on ADAMTS-4/5 expression, chondrogenic human mesenchymal stem cells (hMSCs) and human chondrocytes were transfected with mature miR-92a-3p or an antisense inhibitor (anti-miR-92a-3p), respectively. ADAMTS-4/5 protein production was quantified by enzyme-linked immunosorbent assay (ELISA), and miR92a-3p involvement in IL-1β-mediated catabolic effects was examined by immunoblotting. The roles of activated MAP kinases (MAPK) and nuclear factor (NF)-κB were evaluated by using specific inhibitors. Interaction between miR-92a-3p and its putative binding site in the 3′-untranslated region (3′-UTR) of ADAMTS-4/5 mRNA was confirmed by luciferase reporter assay. Results: miR-92a-3p expression was elevated in chondrogenic hMSCs, with significantly lower expression in OA cartilage than in normal cartilage. Stimulation with IL-1β significantly reduced miR-92a-3p expression in primary human chondrocytes (PHCs). Transfection of chondrocytes with miR-92a-3p downregulated IL-1β-induced ADAMTS-4/5 expression, and the activity of a reporter construct containing the 3′-UTR of human ADAMTS-4/5 mRNA.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes

Mao¹,

Zhang²,

Zhang³

et al. 2017

Cell Physiol Biochem

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“…Particularly p63 might be interesting, because mutations in humans cause skeletal syndromes with digit abnormalities [22] and its overexpression in mice induced accelerated ossifications in long bone digits and tail bones [23]. Moreover, inactivation of miR-92a in zebrafish increased noggin3 expression leading to an inhibition of Bmp signaling and abnormal behavior of chondrogenic progenitors during pharyngeal cartilage formation [24].…”

Section: Discussionmentioning

confidence: 99%

Phenotypic Characterization of miR-92a−/− Mice Reveals an Important Function of miR-92a in Skeletal Development

et al. 2014

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MicroRNAs (miRNAs, miRs) emerged as key regulators of gene expression. Germline hemizygous deletion of the gene that encodes the miR-17∼92 miRNA cluster was associated with microcephaly, short stature and digital abnormalities in humans. Mice deficient for the miR-17∼92 cluster phenocopy several features such as growth and skeletal development defects and exhibit impaired B cell development. However, the individual contribution of miR-17∼92 cluster members to this phenotype is unknown. Here we show that germline deletion of miR-92a in mice is not affecting heart development and does not reduce circulating or bone marrow-derived hematopoietic cells, but induces skeletal defects. MiR-92a−/− mice are born at a reduced Mendelian ratio, but surviving mice are viable and fertile. However, body weight of miR-92a−/− mice was reduced during embryonic and postnatal development and adulthood. A significantly reduced body and skull length was observed in miR-92a−/− mice compared to wild type littermates. µCT analysis revealed that the length of the 5th mesophalanx to 5th metacarpal bone of the forelimbs was significantly reduced, but bones of the hindlimbs were not altered. Bone density was not affected. These findings demonstrate that deletion of miR-92a is sufficient to induce a developmental skeletal defect.

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“…Microinjection and whole-mount in situ hybridization were performed as before [78–81]. Apoptosis were determined by TUNEL assay [82]. WT and p53 mutant zebrafish embryos were injected with object mRNA at one-cell stage and then harvested at 24 hpf for TUNEL labeling using In Situ Cell Death Detection Kit, TMR red (12156792910, Roche) according to the manufacturer’s instruction.…”

Section: Methodsmentioning

confidence: 99%

The Machado–Joseph Disease Deubiquitinase Ataxin-3 Regulates the Stability and Apoptotic Function of p53

Guan

et al. 2016

PLoS Biol

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As a deubiquitinating enzyme (DUB), the physiological substrates of ataxin-3 (ATX-3) remain elusive, which limits our understanding of its normal cellular function and that of pathogenic mechanism of spinocerebellar ataxia type 3 (SCA3). Here, we identify p53 to be a novel substrate of ATX-3. ATX-3 binds to native and polyubiquitinated p53 and deubiquitinates and stabilizes p53 by repressing its degradation through the ubiquitin (Ub)-proteasome pathway. ATX-3 deletion destabilizes p53, resulting in deficiency of p53 activity and functions, whereas ectopic expression of ATX-3 induces selective transcription/expression of p53 target genes and promotes p53-dependent apoptosis in both mammalian cells and the central nervous system of zebrafish. Furthermore, the polyglutamine (polyQ)-expanded ATX-3 retains enhanced interaction and deubiquitination catalytic activity to p53 and causes more severe p53-dependent neurodegeneration in zebrafish brains and in the substantia nigra pars compacta (SNpc) or striatum of a transgenic SCA3 mouse model. Our findings identify a novel molecular link between ATX-3 and p53-mediated cell death and provide an explanation for the direct involvement of p53 in SCA3 disease pathogenesis.

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MicroRNA-92a Upholds Bmp Signaling by Targeting noggin3 during Pharyngeal Cartilage Formation

Cited by 79 publications

References 73 publications

MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes

MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes

Phenotypic Characterization of miR-92a−/− Mice Reveals an Important Function of miR-92a in Skeletal Development

The Machado–Joseph Disease Deubiquitinase Ataxin-3 Regulates the Stability and Apoptotic Function of p53

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