ArticleArthritis & rheumatology (Hoboken, N.J.)2015
MicroRNA-602 and microRNA-608 regulate sonic hedgehog expression via target sites in the coding region in human chondrocytes.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Cross-talk between GLI2 and FOXC1 promotes osteoarthritis-like cartilage catabolism and in vivo joint degeneration.Functional & integrative genomics · 2026Article
- Emerging role of non-coding RNAs in the regulation of Sonic Hedgehog signaling pathway.Cancer cell international · 2022Review
- Epigenetic therapy targeting bone marrow mesenchymal stem cells for age-related bone diseases.Stem cell research & therapy · 2022Review
- Role of the hedgehog signaling pathway in rheumatic diseases: An overview.Frontiers in immunology · 2022Review
- MicroRNA-602 prevents the development of inflammatory bowel diseases in a microbiota-dependent manner.Experimental and therapeutic medicine · 2021Article
- Association of sonic hedgehog signaling pathway genes IHH, BOC, RAB23a and MIR195-5p, MIR509-3-5p, MIR6738-3p with gastric cancer stage.Scientific reports · 2021Article
- Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis.International journal of molecular sciences · 2021Review
- Lysosomal dysfunction in osteoarthritis and aged cartilage triggers apoptosis in chondrocytes through BAX mediated release of Cytochrome c.Osteoarthritis and cartilage · 2021Article
- Sonic Hedgehog Induces Mesenchymal Stromal Cell Senescence-Associated Secretory Phenotype and Chondrocyte Apoptosis in Human Osteoarthritic Cartilage.Frontiers in cell and developmental biology · 2021Article
- Impacts of Green Tea on Joint and Skeletal Muscle Health: Prospects of Translational Nutrition.Antioxidants (Basel, Switzerland) · 2020Review
- MiR-608 Exerts Anti-inflammatory Effects by Targeting ELANE in Monocytes.Journal of clinical immunology · 2020Article
- Advances and challenges in studying noncoding RNA regulation of drug metabolism and development of RNA therapeutics.Biochemical pharmacology · 2019Review
- Naproxen attenuates osteoarthritis progression through inhibiting the expression of prostaglandinl-endoperoxide synthase 1.Journal of cellular physiology · 2019Article
- Epigenetics in osteoarthritis: Novel spotlight.Journal of cellular physiology · 2019Review
- Sonic Hedgehog Signaling Pathway in Endothelial Progenitor Cell Biology for Vascular Medicine.International journal of molecular sciences · 2018Review
- Exonic splice regulation imposes strong selection at synonymous sites.Genome research · 2018Article
- Downregulation of HS6ST2 by miR-23b-3p enhances matrix degradation through p38 MAPK pathway in osteoarthritis.Cell death & disease · 2018Article
- Epigallocatechin-3-O-gallate modulates global microRNA expression in interleukin-1β-stimulated human osteoarthritis chondrocytes: potential role of EGCG on negative co-regulation of microRNA-140-3p and ADAMTS5.European journal of nutrition · 2018Article
- Epigenetics in osteoarthritis: Potential of HDAC inhibitors as therapeutics.Pharmacological research · 2018Review
- Knockdown of PRMT1 suppresses IL-1β-induced cartilage degradation and inflammatory responses in human chondrocytes through Gli1-mediated Hedgehog signaling pathway.Molecular and cellular biochemistry · 2018Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
objectiveHedgehog (HH) signaling has recently been associated with cartilage degradation in osteoarthritis (OA). Because interleukin-1β (IL-1β) has been implicated as a principal instigator of OA, we sought to determine whether IL-1β induces the expression of sonic HH (SHH) and its regulation by microRNAs (miRNAs) in human chondrocytes.
methodsExpression of SHH protein in human OA cartilage and in an animal model of OA was determined by immunohistochemical analysis and immunofluorescence analysis, respectively. Gene and protein expression in IL-1β- or SHH-stimulated OA chondrocytes was determined by TaqMan assays and Western blotting, respectively. The effect of overexpression of miRNA-602 (miR-602) and miR-608 or their antagomirs on SHH expression was evaluated by transient transfection of human chondrocytes and HEK 293 cells. The role of signaling pathways was evaluated using small molecule inhibitors. Binding of miRNAs with the putative seed sequence in SHH messenger RNA (mRNA) was validated using a luciferase reporter assay.
resultsExpression of SHH, patched 1, Gli-1, HH-interacting protein, matrix metalloproteinase 13 (MMP-13), and Colα1(X) was high in damaged OA cartilage. In damaged cartilage and in IL-1β-stimulated OA chondrocytes, expression of SHH was inversely correlated with expression of miR-608. Cotransfection of OA chondrocytes with miR-608 or miR-602 mimic inhibited reporter activity, and mutation of the miRNA seed sequences abolished the repression of reporter activity. Overexpression of miR-602 or miR-608 inhibited the expression of SHH mRNA and protein, and this was abrogated by antagomirs. Stimulation with recombinant human SHH protein up-regulated MMP-13 expression, and inhibition of HH signaling blocked MMP-13 expression in OA chondrocytes.
conclusionMiR-602 and miR-608 are important posttranscription regulators of SHH expression in OA chondrocytes, and their suppression by IL-1β may contribute to the enhanced expression of SHH and MMP-13 in OA.
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