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10.1038/cddis.2017.511

http://scihub22266oqcxt.onion/10.1038/cddis.2017.511
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suck abstract from ncbi


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pmid29022900
      Cell+Death+Dis 2017 ; 8 (10 ): e3109
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  • Increased 15-lipoxygenase-1 expression in chondrocytes contributes to the pathogenesis of osteoarthritis #MMPMID29022900
  • Chen K ; Yan Y ; Li C ; Yuan J ; Wang F ; Huang P ; Qian N ; Qi J ; Zhou H ; Zhou Q ; Deng L ; He C ; Guo L
  • Cell Death Dis 2017[Oct]; 8 (10 ): e3109 PMID29022900 show ga
  • 15-Lipoxygenase-1 (15-LO-1) is involved in many pathological processes. The purpose of this study was to determine the potential role of 15-LO-1 in osteoarthritis (OA). The levels of 15-LO-1 expression were measured by western blotting and quantitative real-time PCR in articular cartilage from the OA rat models and OA patients. To further investigate the effects of 15-LO-1 on chondrocyte functions, such as extracellular matrix (ECM) secretion, the release of matrix-degrading enzymes, the production of reactive oxygen species (ROS), cell proliferation and apoptosis, we decreased or increased 15-LO-1 expression in chondrocytes by means of transfecting with siRNA targeting 15-LO-1 and plasmid encoding 15-LO-1, respectively. The results showed that 15-LO-1 expression was obviously increased in articular cartilage from OA rats and OA patients. It was also found that many factor-related OA, such as mechanical loading, ROS, SNP and inflammatory factor, significantly promoted 15-LO-1 expression and activity in chondrocytes. Silencing 15-LO-1 was able to markedly alleviate mechanical loading-induced cartilage ECM secretion, cartilage-degrading enzyme secretion and ROS production. Overexpression of 15-LO-1 could inhibit chondrocyte proliferation and induce chondrocyte apoptosis. In addition, reduction of 15-LO-1 in vivo significantly alleviated OA. Taken together, these results indicate that 15-LO-1 has an important role in the disease progression of OA. Thus 15-LO-1 may be a good target for developing drugs in the treatment of OA.
  • |Animals [MESH]
  • |Apoptosis/physiology [MESH]
  • |Arachidonate 15-Lipoxygenase/genetics/*metabolism [MESH]
  • |Cartilage, Articular/cytology/*pathology [MESH]
  • |Cell Proliferation/physiology [MESH]
  • |Cells, Cultured [MESH]
  • |Chondrocytes/*metabolism [MESH]
  • |Disease Progression [MESH]
  • |Extracellular Matrix/metabolism [MESH]
  • |Humans [MESH]
  • |Knee Joint/cytology/*pathology [MESH]
  • |Male [MESH]
  • |Osteoarthritis/*pathology [MESH]
  • |RNA Interference [MESH]
  • |RNA, Small Interfering/genetics [MESH]
  • |Rats [MESH]
  • |Rats, Sprague-Dawley [MESH]


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