The regulatory effects of miR-138-5p on selenium deficiency-induced chondrocyte apoptosis are mediated by targeting SelM
- 7 March 2019
- journal article
- research article
- Published by Oxford University Press (OUP) in Metallomics
- Vol. 11 (4), 845-857
- https://doi.org/10.1039/c9mt00006b
Abstract
Apoptosis is a common paradigm of cell death and plays a key role in cartilage damage and selenium (Se) deficiency. Selenoproteins play major roles in determining the biological effects of Se, and are potentially involved in the pathophysiological processes in bone tissue. MicroRNAs (miRNAs) play important roles in cell proliferation, differentiation, apoptosis and tumorigenesis. Based on the preliminary results, the expression of selenoprotein M (SelM) was significantly decreased (69%) in chicken cartilage tissues with Se deficiency, and we subsequently screened and verified that SelM is one of the target genes of miR-138-5p in chicken cartilage using a dual luciferase reporter assay and real-time quantitative PCR (qRT-PCR). The expression of miR-138-5p was increased in response to Se deficiency, and the overexpression of miR-138-5p increased caspase-3, caspase-9, BAX and BAK levels, while the BCL-2 level was decreased, suggesting that miR-138-5p induced apoptosis via the mitochondrial pathway in vivo and in vitro. We explored whether oxidative stress, mitochondrial fission and fusion, and energy metabolism might trigger apoptosis to obtain an understanding of the mechanisms underlying the effects of miR-138-5p on Se deficiency-induced apoptosis in cartilage. The levels of indicators of oxidative stress, mitochondrial dynamics and energy metabolism were changed as well. This study confirmed that SelM is one of the target genes of miR-138-5p, and the overexpression of miR-138-5p induced by Se deficiency triggered oxidative stress, an imbalance in mitochondrial fission and fusion, and energy metabolism dysfunction. Therefore, miR-138-5p is involved in the mitochondrial apoptosis pathway via targeting SelM in chicken chondrocytes.Keywords
Funding Information
- National Natural Science Foundation of China (31320103920, 31872437)
- National Natural Science Foundation of China (31320103920, 31872437)
This publication has 45 references indexed in Scilit:
- Deletion of Selenoprotein M Leads to Obesity without Cognitive DeficitsJournal of Biological Chemistry, 2013
- Effect of oxygen free radicals and nitric oxide on apoptosis of immune organ induced by selenium deficiency in chickensBioMetals, 2013
- Hypoxia, RONS and energy metabolism in articular cartilageOsteoarthritis and Cartilage, 2010
- Silencing microRNA-34a inhibits chondrocyte apoptosis in a rat osteoarthritis model in vitroRheumatology, 2010
- The Neuroprotective Functions of Selenoprotein M and its Role in Cytosolic Calcium RegulationAntioxidants and Redox Signaling, 2010
- Osteo-Chondroprogenitor–Specific Deletion of the Selenocysteine tRNA Gene, Trsp, Leads to Chondronecrosis and Abnormal Skeletal Development: A Putative Model for Kashin-Beck DiseasePLoS Genetics, 2009
- ERK activation induced by selenium treatment significantly downregulates β/γ-secretase activity and Tau phosphorylation in the transgenic rat overexpressing human selenoprotein MInternational Journal of Molecular Medicine, 2009
- Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissuesOncogene, 2005
- Selenium Deficiency-Induced Growth Retardation Is Associated with an Impaired Bone Metabolism and OsteopeniaJournal of Bone and Mineral Research, 2001
- Osteoarthrosis induced by intra‐articular hydrogen peroxide injection and running loadJournal of Orthopaedic Research, 1990