title: Genome-wide gene expression analysis suggests an important role of hypoxia in the pathogenesis of endemic osteochondropathy Kashin-Beck disease.
abstract: Kashin-Beck Disease (KBD) is an endemic osteochondropathy, the pathogenesis of which remains unclear now. In this study, we compared gene expression profiles of articular cartilage derived respectively from KBD patients and normal controls. Total RNA were isolated, amplified, labeled and hybridized to Agilent human 1A 22 k whole genome microarray chip. qRT-PCR was conducted to validate our microarray data. We detected 57 up-regulated genes (ratios ≥2.0) and 24 down-regulated genes (ratios ≤0.5) in KBD cartilage. To further identify the key genes involved in the pathogenesis of KBD, Bayesian analysis of variance for microarrays (BAM) software was applied and identified 12 potential key genes with an average ratio 6.64, involved in apoptosis, metabolism, cytokine & growth factor and cytoskeleton & cell movement. Gene Set Enrichment Analysis (GSEA) software was used to identify differently expressed gene ontology categories and pathways. GSEA found that a set of apoptosis, hypoxia and mitochondrial function related gene ontology categories and pathways were significantly up-regulated in KBD compared to normal controls. Based on the results of this study, we suggest that chronic hypoxia-induced mitochondrial damage and apoptosis might play an important role in the pathogenesis of KBD. Our efforts may help to understand the pathogenesis of KBD as well as other osteoarthrosis with similar articular cartilage lesions.
authors.affiliation: Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Faculty of Public Health, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China. fzhxjtu@mail.xjtu.edu.cn
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Xiong
authors.initials: X
authors.lastname: Guo
authors.forename: Weizhuo
authors.initials: W
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Yan
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D019353:Endemic Diseases; D005260:Female; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D000860:Hypoxia; D057767:Kashin-Beck Disease / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010007:Osteochondritis / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger