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Cryptotanshinone (CTS) has emerged as an anti-inflammatory agent in osteoarthritis (OA). However, the molecular mechanism underlying its potent therapeutic effect on OA remains largely unknown. MicroRNAs (miRNAs) act as crucial regulators in maintaining cartilage homeostasis. To investigate whether CTS protects against developing OA through regulation of miRNAs, we examined the potential CTS-mediated miRNA molecules using microarray analysis. We found that CTS significantly promoted miR-106a-5p expression in chondrocytes. Using the OA mouse model created by anterior cruciate ligament transection, we revealed that intra-articular injection of miR-106a-5p agomir attenuated OA. In addition, miR-106a-5p inhibited GLI-similar 3 (GLIS3) production by directly targeting the 3' untranslated region. CTS promoted miR-106a-5p expression through recruitment of a member of the paired box (PAX) family of transcription factors, PAX5, to the miR-106a-5p promoter. Inhibition of PAX5 mimicked the effect of miR-106a-5p and abolished the CTS ability to regulate miR-106a-5p expression. In OA patients, miR-106-5p is downregulated which is accompanied by downregulation of PAX5 and upregulation of GLIS3. Collectively, these data highlight that the PAX5/miR-106a-5p/GLIS3 axis acts as a novel pleiotropic regulator in CTS-mediated OA cartilage protection, suggesting that miR-106a-5p and PAX5 activation and GLIS3 inhibition might be useful and attractive for therapeutic strategies to treat OA patients.
Pubmed ID: 29858052
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A division of Applied Biosystems selling products for the isolation, detection, quantification, amplification, and characterization of RNA.
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsA commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.
View all literature mentionsAffymetrix has recently released a new software for the acquisition, management, and analysis of gene expression data. The new GeneChip Operating Software (GCOS) platform enables researchers to perform gene expression, SNP mapping and resequencing analysis with integrated data management and scalable client server configurations. * Compatible with additional Affymetrix analysis software such as Data Mining Tool (DMT) and GeneChip DNA Analysis Software (GDAS) * Supports Gene Expression, Resequencing and Genotyping Applications * Baseline Comparison Analysis Input: Affymetrix .DAT file Output: Affymetrix files (.CEL, .CHP, .RPT, .EXP, .TXT) Availability: The Core Facility has a copy of GCOS, as well as an older version of the Affymetrix software, Microarray Suite (MAS), available for use upon request.
View all literature mentionsAn integrated database of positional relationships between animal miRNAs and genomic annotation sets and animal miRNA targets according to combinations of widely used target prediction programs. miRGen has three connected interfaces which query this data. The Genomics interface allows the user to explore where whole-genome collections of miRNAs are located with respect to UCSC genome browser annotation sets such as Known Genes, Refseq Genes, Genscan predicted genes, CpG islands, and pseudogenes. The Targets interface provides access to unions and intersections of four widely used target prediction programs, and experimentally supported targets from TarBase. The Clusters interface provides predicted miRNA clusters at any given inter-miRNA distance, and provides specific functional information on the targets of miRNAs within each cluster.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
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