Peroxisomal dysfunction is associated with up-regulation of apoptotic cell death via miR-223 induction in knee osteoarthritis patients with type 2 diabetes mellitus

被引:29
作者
Kim, Dongkyun [1 ]
Song, Jinsoo [1 ]
Ahn, Chihyun [1 ]
Kang, Yeonho [1 ]
Chun, Churl-Hong [2 ]
Jin, Eun-Jung [1 ]
机构
[1] Wonkwang Univ, Coll Nat Sci, Dept Biol Sci, Iksan 570749, Chunbuk, South Korea
[2] Wonkwang Univ, Sch Med, Dept Orthoped Surg, Iksan 570749, Chunbuk, South Korea
基金
新加坡国家研究基金会;
关键词
Peroxisome dysfunction; Osteoarthritis; Diabetes mellitus; PEX-16; miR-223; MICRORNAS; MITOCHONDRIA; PATHOGENESIS; PREVALENCE; MUTATION; OBESITY; ABSENCE; PEX16;
D O I
10.1016/j.bone.2014.04.001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:124 / 131
页数:8
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