Abstract
Osteoarthritis (OA) is a joint disease resulting in high rates of disability and low quality of life. The initial site of OA (bone or cartilage) is uncertain. The aim of the current study was to explore biomarkers and pathological processes in subchondral bone samples. The gene expression profile GSE51588 was downloaded from the Gene Expression Omnibus database. Fifty subchondral bone [knee lateral tibial (LT) and medial tibial (MT)] samples from 40 OA and 10 non-OA subjects were analyzed. After data preprocessing, 5439 genes were obtained for weighted gene co-expression network analysis. Highly correlated genes were divided into 19 modules. The yellow module was found to be highly correlated with OA (r = 0.71, p = 1e-08) and the brown module was most associated with the differences between the LT and MT regions (r = 0.77, p = 1e-10). Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment indicated that the yellow module was enriched in a variety of components including proteinaceous extracellular matrix and collagen trimers, involved in protein digestion and absorption, axon guidance, ECM-receptor interaction, and the PI3K-Akt signaling pathway. In addition, the brown module suggests that the differences between the early (LT) and end (MT) stage of OA are associated with extracellular processes and lipid metabolism. Finally, 45 hub genes in the yellow module (COL24A1, COL5A2, COL3A1, MMP2, COL6A1, etc.) and 72 hub genes in the brown module (LIPE, LPL, LEP, SLC2A4, FABP4, ADH1B, ALDH4A1, ADIPOQ, etc.) were identified. Hub genes were validated using samples from cartilage (GSE57218). In summary, 45 hub genes and 72 hub genes in two modules are associated with OA. These hub genes could provide new biomarkers and drug targets in OA. Further studies focusing on subchondral bone are required to validate these hub genes and better understand the pathological process of OA.
Highlights
Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease, primarily involving large weight-bearing joints in the hip and the knee (Valdes and Spector, 2011; Ryd et al, 2015)
The soft-thresholding parameter was determined as β = 12 where the curve first reached R2 = 0.85, to construct a weighted network based on a scale-free topology criterion (Figure 2)
After data set preprocessing, weighted gene network construction, and module identification, relating modules to traits and functional enrichment, we found that both the yellow and brown modules were associated with the occurrence of OA
Summary
Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease, primarily involving large weight-bearing joints in the hip and the knee (Valdes and Spector, 2011; Ryd et al, 2015). Biomarkers for Osteoarthritis (Centers for Disease Control and Prevention [Cdc], 2009). Osteoarthritis is characterized by a complex pathological process including progressive cartilage erosion, osteophyte formation, subchondral bone modification, and synovial inflammation. It involves a long disease span of approximately to 20 years from onset to the end-stage, when joint replacement is recognized as the most effective treatment (Chu et al, 2014). An analysis of gene expression microarray profiling of subchondral bone samples could contribute to the identification of new biomarkers and increase the mechanistic understanding necessary to provide early prevention and management of OA (Vukusic et al, 2013)
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