OBJECTIVE: To define for the first time the transcriptomes of normal and end-stage osteoarthritis (OA) hip cartilage. MATERIALS AND METHODS: RNA was isolated from cartilage within 2h of joint replacement surgery. Gene expression was analyzed using Agilent GeneSpring GX 11 following hybridization to Illumina Human HT-12 V3 microarrays. Real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to validate the expression of six genes identified by microarray as differentially expressed. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) were used to investigate enriched functions or canonical pathways amongst differentially expressed genes respectively. RESULTS: In total we identified 998 differentially expressed genes (fold change ≥ ±1.5, P-value ≤ 0.01) between neck of femur fracture (NOF) (n = 10) and OA hip (n = 9) patient cartilage. These differentially expressed genes were enriched within 71 canonical pathways. A comparison between a comparable knee dataset(20) only identified 229 genes similarly differentially expressed although remarkably 34 canonical pathways overlapped between experiments. CONCLUSIONS: This study is the first to report a comprehensive gene expression analysis of human hip OA cartilage compared to control (NOF) cartilage at the whole-genome level. Our differential gene expression dataset shows excellent correlation with similar defined studies using comparable tissue but reveals discord between hip and knee OA at the individual gene status but with commonality with regards the molecular pathways involved.
OBJECTIVE: To define for the first time the transcriptomes of normal and end-stage osteoarthritis (OA) hip cartilage. MATERIALS AND METHODS: RNA was isolated from cartilage within 2h of joint replacement surgery. Gene expression was analyzed using Agilent GeneSpring GX 11 following hybridization to Illumina Human HT-12 V3 microarrays. Real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to validate the expression of six genes identified by microarray as differentially expressed. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) were used to investigate enriched functions or canonical pathways amongst differentially expressed genes respectively. RESULTS: In total we identified 998 differentially expressed genes (fold change ≥ ±1.5, P-value ≤ 0.01) between neck of femur fracture (NOF) (n = 10) and OA hip (n = 9) patient cartilage. These differentially expressed genes were enriched within 71 canonical pathways. A comparison between a comparable knee dataset(20) only identified 229 genes similarly differentially expressed although remarkably 34 canonical pathways overlapped between experiments. CONCLUSIONS: This study is the first to report a comprehensive gene expression analysis of human hip OA cartilage compared to control (NOF) cartilage at the whole-genome level. Our differential gene expression dataset shows excellent correlation with similar defined studies using comparable tissue but reveals discord between hip and knee OA at the individual gene status but with commonality with regards the molecular pathways involved.
Authors: Unnur Styrkarsdottir; Hannes Helgason; Asgeir Sigurdsson; Gudmundur L Norddahl; Arna B Agustsdottir; Louise N Reynard; Amanda Villalvilla; Gisli H Halldorsson; Aslaug Jonasdottir; Audur Magnusdottir; Asmundur Oddson; Gerald Sulem; Florian Zink; Gardar Sveinbjornsson; Agnar Helgason; Hrefna S Johannsdottir; Anna Helgadottir; Hreinn Stefansson; Solveig Gretarsdottir; Thorunn Rafnar; Ina S Almdahl; Anne Brækhus; Tormod Fladby; Geir Selbæk; Farhad Hosseinpanah; Fereidoun Azizi; Jung Min Koh; Nelson L S Tang; Maryam S Daneshpour; Jose I Mayordomo; Corrine Welt; Peter S Braund; Nilesh J Samani; Lambertus A Kiemeney; L Stefan Lohmander; Claus Christiansen; Ole A Andreassen; Olafur Magnusson; Gisli Masson; Augustine Kong; Ingileif Jonsdottir; Daniel Gudbjartsson; Patrick Sulem; Helgi Jonsson; John Loughlin; Thorvaldur Ingvarsson; Unnur Thorsteinsdottir; Kari Stefansson Journal: Nat Genet Date: 2017-03-20 Impact factor: 38.330
Authors: Muhammad Farooq Rai; Linda J Sandell; Toby N Barrack; Lei Cai; Eric D Tycksen; Simon Y Tang; Matthew J Silva; Robert L Barrack Journal: Cartilage Date: 2018-09-03 Impact factor: 4.634
Authors: K M Fisch; R Gamini; O Alvarez-Garcia; R Akagi; M Saito; Y Muramatsu; T Sasho; J A Koziol; A I Su; M K Lotz Journal: Osteoarthritis Cartilage Date: 2018-08-03 Impact factor: 6.576