title: Peroxisomal dysfunction is associated with up-regulation of apoptotic cell death via miR-223 induction in knee osteoarthritis patients with type 2 diabetes mellitus.
abstract: 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.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk, 570-749, Republic of Korea.
authors.forename: Dongkyun
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk, 570-749, Republic of Korea.
authors.forename: Jinsoo
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk, 570-749, Republic of Korea.
authors.forename: Chihyun
authors.initials: C
authors.lastname: Ahn
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk, 570-749, Republic of Korea.
authors.forename: Yeonho
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Orthopedic Surgery, Wonkwang University School of Medicine, Iksan, Chunbuk, 570-749, Republic of Korea.
authors.forename: Churl-Hong
authors.initials: CH
authors.lastname: Chun
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk, 570-749, Republic of Korea. Electronic address: jineunjung@wku.ac.kr.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Jin
mesh_terms: D017209:Apoptosis; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D020675:Peroxisomes / Q000502:physiology*; D016133:Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; C525067:MIR223, human
keywords: Diabetes mellitus; Osteoarthritis; PEX-16; Peroxisome dysfunction; miR-223