title: Analysis of altered microRNA expression profile in the reparative interface of the femoral head with osteonecrosis.
abstract: The reparative reaction is considered to be important during the occurrence of collapse in the femoral head with osteonecrosis (ONFH), but little is known about the long-term reparative process. The aim of this study was to determine and analyze the altered microRNA expression profile in the reparative interface of ONFH, and further validate the expression of the involved genes in the predicted pathways. Microarray analysis was performed comparing the reparative interface of patients with ONFH and normal tissue of patients with fresh femoral neck fracture (FNF) and partly validated by real-time PCR. Potential target genes of differentially expressed miRNAs were predicted by TargetScan and miRanda, and the target genes were used for further bioinformatics analysis such as Gene Ontology and Pathway assay. The filtered miRNAs and genes in the predict pathways were further examined by real-time PCR in another 6 independent ONFH patients. Among the 2578 miRNAs identified, 17 were consistently differentially expressed, 12 of which are up-regulated and 5 down-regulated. GO classification showed that the predicted target genes of these miRNAs are involved in signal transduction, cell differentiation, methylation, cell growth and apoptosis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) classification indicated that these genes play a role in angiogenesis and Wnt signaling pathways. The expression of miR-34a and miR-146a and genes in the predict pathways were significantly up-regulated. This study presented a global view of miRNA expression in the reparative interface of osteonecrosis. In addition, our data provided novel and robust information for further researches in the pathogenesis and molecular events of ONFH.
authors.affiliation: Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Cancer Biology, Mayo Clinic, FL, USA.
authors.forename: Heng-feng
authors.initials: HF
authors.lastname: Yuan
authors.affiliation: Department of Cancer Biology, Mayo Clinic, FL, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Von Roemeling
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Hui-di
authors.initials: HD
authors.lastname: Gao
authors.affiliation: Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Chang-an
authors.initials: CA
authors.lastname: Guo
authors.affiliation: Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: zuoqin_yan@163.com.
authors.forename: Zuo-qin
authors.initials: ZQ
authors.lastname: Yan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D019644:Arthroplasty, Replacement, Hip; D016723:Bone Remodeling / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D005270:Femur Head / Q000503:physiopathology*; D017102:Fracture Healing / Q000502:physiology*; D020869:Gene Expression Profiling; D006621:Hip Joint / Q000502:physiology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010010:Osteoclasts / Q000378:metabolism; D010020:Osteonecrosis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000235:genetics; D055815:Young Adult
chemical_list: C542542:MIRN146 microRNA, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs
keywords: Femoral head; Genes; MicroRNA; Osteonecrosis; Reparative interface