title: Gene expression analysis suggests bone development-related genes GDF5 and DIO2 are involved in the development of Kashin-Beck disease in children rather than adults.
abstract: OBJECTIVE
  To investigate the differences in gene expression between children and adults with Kashin-Beck disease (KBD).
  
  
  METHODS
  12 children with KBD and 12 healthy children were selected and divided into 4 KBD vs. control pairs matched according to age and gender, with each pair having 3 KBD children and 3 healthy children. Additionally, 15 adults with KBD and 15 healthy adults were selected and divided into 5 KBD vs. control pairs matched according to age and gender, with each pair having 3 KBD adults and 3 healthy adults. Total RNA was isolated from peripheral blood mononuclear cells (PBMCs) respectively. A total of 367 target genes were selected based on previous genome-wide gene expression profile analysis. Expression levels of the 367 genes were evaluated by customized oligonucleotide microarray and the differentially expressed genes were identified. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was conducted to validate the microarray data.
  
  
  RESULTS
  A total of 95 (25.9%) genes in KBD children and 158 (43.1%) genes in KBD adults were found to exhibit more than two-fold change in gene expression level relative to healthy controls. By comparing differentially expressed genes identified in KBD children to those of KBD adults, 42 genes were found to be differentially expressed only in KBD children. And 105 genes were found to be differentially expressed only in KBD adults. Further, 16 differentially expressed genes common to both KBD children and adults were found to be asynchronously expressed in KBD children compared to KBD adults.
  
  
  CONCLUSIONS
  Significant differences in gene expression pattern were identified between KBD children and KBD adults, indicating different molecular mechanisms underlying cartilage lesions of KBD children and KBD adults. In addition, bone development-related genes GDF5 (expression ratio = 2.14±0.02) and DIO2 (expression ratio = 0.11±0.05) may contribute to the development of KBD in children rather than in adults.
authors: School of Public Health, Health Science Center, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases of Ministry Health, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors: Yan
authors: Y
authors: Wen
authors: School of Public Health, Health Science Center, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases of Ministry Health, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors: Feng
authors: F
authors: Zhang
authors: School of Public Health, Health Science Center, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases of Ministry Health, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors: Chunyan
authors: C
authors: Li
authors: School of Public Health, Health Science Center, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases of Ministry Health, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors: Shulan
authors: S
authors: He
authors: School of Public Health, Health Science Center, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases of Ministry Health, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors: Wuhong
authors: W
authors: Tan
authors: School of Public Health, Health Science Center, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases of Ministry Health, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors: Yanxia
authors: Y
authors: Lei
authors: Department of Kashin-Beck Diseases, Qinghai Institute for Endemic Disease Control and Prevention, Xining, Qinghai, P. R. China.
authors: Qiang
authors: Q
authors: Zhang
authors: National Engineering Research Center for Miniaturized Detection Systems, Northwest University, Xi'an, Shaanxi, P. R. China.
authors: Hanjie
authors: H
authors: Yu
authors: School of Public Health, Health Science Center, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases of Ministry Health, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors: Jingjing
authors: J
authors: Zheng
authors: School of Public Health, Health Science Center, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases of Ministry Health, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors: Xiong
authors: X
authors: Guo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001842:Bone and Bones / Q000000981:diagnostic imaging; D002648:Child; D005260:Female; D055428:Growth Differentiation Factor 5 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D057767:Kashin-Beck Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D011859:Radiography; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D055428:Growth Differentiation Factor 5; D007453:Iodide Peroxidase; D000097564:Iodothyronine Deiodinase Type II; C525893:GDF5 protein, human