Identification of genes involved in the effects of hypoxia-inducible
factor-2 on articular chondrocytes using bioinformatic analysis and
validation in osteoarthritis
Abstract
Although over-expression of hypoxia-inducible factor-2 alpha (HIF-2α)
can result in cartilage destruction and osteoarthritis (OA) development,
the underlying mechanisms remain poorly understood. Here, we
investigated the molecular mechanisms in chondrocytes over-expressing
HIF-2α. The GeneCloud of Biotechnology Information platform was used to
identify differentially expressed genes (DEGs). Using the GEO GSE104794
dataset of control (empty adenovirus, n = 4) and experimental
(recombinant adenovirus expressing HIF-2α, n = 4) groups, we performed
DEG, Gene Ontology, pathway, pathway network, and gene signal network
analyses. Similarly, DEG analysis was performed for the GEO GSE51588
dataset of control (non-OA, n = 4) and experimental (OA, n = 20) groups.
Thereafter, intersection of GSE104794 gene signal network analysis and
GSE51588 DEG analysis was performed for the key genes, validated by
quantitative reverse transcription-polymerase chain reaction. A total of
542 DEGs were identified, among which, the 10 most significant genes in
the gene signal network were Nfkb1, Tlr2, Nt5e, Enpp1, Entpd3, Vegfa,
Ptgs2, Socs3, Fos, and Epas1. The key genes in OA were LUM, ENTPD3,
SMPD3, FGFR3, GPX3, IRAK3, EREG, HTR2A, TLR2, and CDA. Taken together,
we screened key genes that are potentially involved in osteoarthritis,
thereby providing a basis for identifying valuable markers for this
disease.