期刊
BONE
卷 64, 期 -, 页码 124-131出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2014.04.001
关键词
Peroxisome dysfunction; Osteoarthritis; Diabetes mellitus; PEX-16; miR-223
资金
- National Research Foundation (NRF) 333 of Korea Grant - Korean Governments by the Ministry of 334 Education [2013R1A2A2A0167194, 2012R1A1A2039074]
- MSIP [2013R1A1A2011999, 2011-0030130]
- National Research Foundation of Korea [2012R1A1A2039074] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Recent increasing evidences showing the interconnection between mitochondria and peroxisome in performing metabolic functions imply that peroxisome dysfunction could lead to a wide variety of human diseases including cancer and osteoarthritis (OA) as mitochondria dysfunction. Even though there is a higher incidence and development of OA in diabetes mellitus (DM) patients, there is not much evidential mechanism study in this inter-regulation between OA and OA with DM in a new view of peroxisome. In this study, we analyzed the alteration of peroxisomal gene expression that could responsible for pathological difference between OA chondrocytes and OA/DM chondrocytes. To discriminate responsible genes in the OA/DM pathogenesis, the expressions of three hundred sixty-two genes reported to differentially relate to peroxisome were analyzed with OA chondrocytes in OA cartilage and OA/DM chondrocytes in the cartilage of OA with DM patient Among them, PEX-16, a component of peroxisome, was significantly down-regulated in OA/DM chondrocytes and this down-regulation of PEX-16 increased the miR-223 induction. Knockdown studies using PEX-16 null cell line and PEX-16 specific siRNA showed the significant increase in apoptotic cell death. Moreover, over-expression of miR-223 stimulates apoptotic cell death in human articular chondrocytes and induced severe cartilage destruction in db/db mice. In conclusion, our study showed the differential peroxisomal gene expression profiles for OA/DM chondrocytes from OA chondrocytes and suggests the possibility that peroxisomal dysfunction in OA/DM could be responsible for early incidence and development of OA in DM patients. (C) 2014 Elsevier Inc. All rights reserved.
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