title: Mitochondrial genome sequencing of chondrocytes in osteoarthritis by human mitochondria RT2 Profiler™ PCR array.
abstract: Mitochondria are not only the main energy generators of the cell, but also             mediate several critical biochemical processes such as apoptosis, proliferation             and redox homeostasis. As such, mitochondrial dysfunctions can lead to a wide             variety of human diseases, including cancer and osteoarthritis (OA). In OA, mitochondrial-associated             signaling has been implicated in the molecular events leading to cartilage degradation,             including oxidative stress, defective chondrocyte biosynthesis and growth responses,             increased cytokine-induced chondrocyte inflammation and matrix catabolism, cartilage             matrix calcification and increased chondrocyte apoptosis. Thus, the mitochondrial             genome represents an attractive target for molecular therapy and OA research has             focused on determining its role in chondrocyte metabolism and subsequent cartilage             degradation. In this study, we analyzed the mitochondrial gene expression changes             that characterize chondrocytes in OA using the Human Mitochondria RT² Profiler™             PCR Array. Twenty-six differentially expressed genes were identified that discriminated             chondrocytes in OA from those in normal cartilage, including 17 upregulated and             9 downregulated genes. These genes represent diverse functional categories, including             mitochondrial membrane polarization and potential, mitochondrial transport, small             molecule transport, targeting proteins to the mitochondria, mitochondrial protein             import, outer and inner membrane translocation, mitochondrial fission and fusion,             mitochondrial localization and apoptosis. Western blot analysis confirmed that             the p53 upregulated modulator of apoptosis (PUMA; encoded by the BB3 gene) was             significantly upregulated in OA cartilage. In conclusion, our study generates             a differential mitochondrial gene expression profile for chondrocytes in OA and             demonstrates that mitochondrial genome dysregulation occurs in cartilage cells             during OA. Finally, our results indicate that PUMA may be a new diagnostic and             therapeutic target for OA.
authors.affiliation: Department of Orthopaedics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, PR China.
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Shen
authors.forename: Yuxian
authors.initials: Y
authors.lastname: Chen
authors.forename: Janying
authors.initials: J
authors.lastname: Pan
authors.forename: Hua
authors.initials: H
authors.lastname: Zeng
authors.forename: Hang
authors.initials: H
authors.lastname: Fang
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ye
authors.forename: Chun
authors.initials: C
authors.lastname: Zeng
authors.forename: Rongkai
authors.initials: R
authors.lastname: Zhang
authors.forename: Daozhang
authors.initials: D
authors.lastname: Cai
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002358:Cartilage, Articular / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054629:Genome, Mitochondrial; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D011518:Proto-Oncogene Proteins