title: Microarray‑based screening of differentially expressed genes in glucocorticoid‑induced avascular necrosis.
abstract: The underlying mechanisms of glucocorticoid (GC)‑induced avascular necrosis of the femoral head (ANFH) have yet to be fully understood, in particular the mechanisms associated with the change of gene expression pattern. The present study aimed to identify key genes with a differential expression pattern in GC‑induced ANFH. E‑MEXP‑2751 microarray data were downloaded from the ArrayExpress database. Differentially expressed genes (DEGs) were identified in 5 femoral head samples of steroid‑induced ANFH rats compared with 5 placebo‑treated rat samples. Gene Ontology (GO) and pathway enrichment analyses were performed upon these DEGs. A total 93 DEGs (46 upregulated and 47 downregulated genes) were identified in GC‑induced ANFH samples. These DEGs were enriched in different GO terms and pathways, including chondrocyte differentiation and detection of chemical stimuli. The enrichment map revealed that skeletal system development was interconnected with several other GO terms by gene overlap. The literature mined network analysis revealed that 5 upregulated genes were associated with femoral necrosis, including parathyroid hormone receptor 1 (PTHR1), vitamin D (1,25‑Dihydroxyvitamin D3) receptor (VDR), collagen, type II, α1, proprotein convertase subtilisin/kexin type 6 and zinc finger protein 354C (ZFP354C). In addition, ZFP354C and VDR were identified to transcription factors. Furthermore, PTHR1 was revealed to interact with VDR, and α‑2‑macroglobulin (A2M) interacted with fibronectin 1 (FN1) in the PPI network. PTHR1 may be involved in GC‑induced ANFH via interacting with VDR. A2M may also be involved in the development of GC‑induced ANFH through interacting with FN1. An improved understanding of the molecular mechanisms underlying GC‑induced ANFH may provide novel targets for diagnostics and therapeutic treatment.
authors.affiliation: Department of Orthopaedics, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Gangyong
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Orthopaedics, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Guanglei
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedics, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Orthopaedics, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Siqun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Orthopaedics, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Feiyan
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Jingshen
authors.initials: J
authors.lastname: Shi
mesh_terms: D019295:Computational Biology; D030561:Databases, Nucleic Acid; D005271:Femur Head Necrosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D005938:Glucocorticoids / Q000009:adverse effects*; D006801:Humans; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D059467:Transcriptome
chemical_list: D005938:Glucocorticoids