Gene Expression Signature in Endemic Osteoarthritis by Microarray Analysis
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. CONCLUSION 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.