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Bone & Joint Research
Vol. 5, Issue 12 | Pages 594 - 601
1 Dec 2016
Li JJ Wang BQ Fei Q Yang Y Li D

Objectives. In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis. Methods. We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs. Results. A total of three microarray studies were selected for integrated analysis. In all, 1125 genes were found to be significantly differentially expressed between osteoporosis patients and normal controls, with 373 upregulated and 752 downregulated genes. Positive regulation of the cellular amino metabolic process (gene ontology (GO): 0033240, false discovery rate (FDR) = 1.00E + 00) was significantly enriched under the GO category for biological processes, while for molecular functions, flavin adenine dinucleotide binding (GO: 0050660, FDR = 3.66E-01) and androgen receptor binding (GO: 0050681, FDR = 6.35E-01) were significantly enriched. DEGs were enriched in many osteoporosis-related signalling pathways, including those of mitogen-activated protein kinase (MAPK) and calcium. Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57). Conclusion. Analysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. Moreover, significantly enriched pathways, such as MAPK and calcium, may involve in osteoporosis through osteoblastic differentiation and bone formation. Cite this article: J. J. Li, B. Q. Wang, Q. Fei, Y. Yang, D. Li. Identification of candidate genes in osteoporosis by integrated microarray analysis. Bone Joint Res 2016;5:594–601. DOI: 10.1302/2046-3758.512.BJR-2016-0073.R1


Aims. This study aimed to uncover the hub long non-coding RNAs (lncRNAs) differentially expressed in osteoarthritis (OA) cartilage using an integrated analysis of the competing endogenous RNA (ceRNA) network and co-expression network. Methods. Expression profiles data of ten OA and ten normal tissues of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). The differentially expressed messenger RNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the edgeR package. We integrated human microRNA (miRNA)-lncRNA/mRNA interactions with DElncRNA/DEmRNA expression profiles to construct a ceRNA network. Likewise, lncRNA and mRNA expression profiles were used to build a co-expression network with the WGCNA package. Potential hub lncRNAs were identified based on an integrated analysis of the ceRNA network and co-expression network. StarBase and Multi Experiment Matrix databases were used to verify the lncRNAs. Results. We detected 1,212 DEmRNAs and 49 DElncRNAs in OA and normal knee cartilage. A total of 75 dysregulated lncRNA-miRNA interactions and 711 dysregulated miRNA-mRNA interactions were obtained in the ceRNA network, including ten DElncRNAs, 69 miRNAs, and 72 DEmRNAs. Similarly, 1,330 dysregulated lncRNA-mRNA interactions were used to construct the co-expression network, which included ten lncRNAs and 407 mRNAs. We finally identified seven hub lncRNAs, named MIR210HG, HCP5, LINC00313, LINC00654, LINC00839, TBC1D3P1-DHX40P1, and ISM1-AS1. Subsequent enrichment analysis elucidated that these lncRNAs regulated extracellular matrix organization and enriched in osteoclast differentiation, the FoxO signalling pathway, and the tumour necrosis factor (TNF) signalling pathway in the development of OA. Conclusion. The integrated analysis of the ceRNA network and co-expression network identified seven hub lncRNAs associated with OA. These lncRNAs may regulate extracellular matrix changes and chondrocyte homeostasis in OA progress. Cite this article:Bone Joint Res. 2020;9(3):90–98


Bone & Joint Research
Vol. 7, Issue 5 | Pages 343 - 350
1 May 2018
He A Ning Y Wen Y Cai Y Xu K Cai Y Han J Liu L Du Y Liang X Li P Fan Q Hao J Wang X Guo X Ma T Zhang F

Aim. Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage. Patients and Methods. Genome-wide DNA methylation profiling of articular cartilage from five patients with OA of the knee and five healthy controls was conducted using the Illumina Infinium HumanMethylation450 BeadChip (Illumina, San Diego, California). Other independent genome-wide mRNA expression profiles of articular cartilage from three patients with OA and three healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Integrative pathway enrichment analysis of DNA methylation and mRNA expression profiles was performed using integrated analysis of cross-platform microarray and pathway software. Gene ontology (GO) analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results. We identified 1265 differentially methylated genes, of which 145 are associated with significant changes in gene expression, such as DLX5, NCOR2 and AXIN2 (all p-values of both DNA methylation and mRNA expression < 0.05). Pathway enrichment analysis identified 26 OA-associated pathways, such as mitogen-activated protein kinase (MAPK) signalling pathway (p = 6.25 × 10-4), phosphatidylinositol (PI) signalling system (p = 4.38 × 10-3), hypoxia-inducible factor 1 (HIF-1) signalling pathway (p = 8.63 × 10-3 pantothenate and coenzyme A (CoA) biosynthesis (p = 0.017), ErbB signalling pathway (p = 0.024), inositol phosphate (IP) metabolism (p = 0.025), and calcium signalling pathway (p = 0.032). Conclusion. We identified a group of genes and biological pathwayswhich were significantly different in both DNA methylation and mRNA expression profiles between patients with OA and controls. These results may provide new clues for clarifying the mechanisms involved in the development of OA. Cite this article: A. He, Y. Ning, Y. Wen, Y. Cai, K. Xu, Y. Cai, J. Han, L. Liu, Y. Du, X. Liang, P. Li, Q. Fan, J. Hao, X. Wang, X. Guo, T. Ma, F. Zhang. Use of integrative epigenetic and mRNA expression analyses to identify significantly changed genes and functional pathways in osteoarthritic cartilage. Bone Joint Res 2018;7:343–350. DOI: 10.1302/2046-3758.75.BJR-2017-0284.R1


Bone & Joint Open
Vol. 4, Issue 1 | Pages 13 - 18
5 Jan 2023
Walgrave S Oussedik S

Abstract

Robotic-assisted total knee arthroplasty (TKA) has proven higher accuracy, fewer alignment outliers, and improved short-term clinical outcomes when compared to conventional TKA. However, evidence of cost-effectiveness and individual superiority of one system over another is the subject of further research. Despite its growing adoption rate, published results are still limited and comparative studies are scarce. This review compares characteristics and performance of five currently available systems, focusing on the information and feedback each system provides to the surgeon, what the systems allow the surgeon to modify during the operation, and how each system then aids execution of the surgical plan.

Cite this article: Bone Jt Open 2023;4(1):13–18.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 271 - 271
1 May 2009
Betti E Riani E Vitale M Bigliazzi N Vaglini M
Full Access

Aims: The choice of the treatment of tibial plateau fractures remains a controversial topic in current traumatology practice. The best treatment must have three fundamental requirements: to be less invasive as possible, to result in a good reduction, to have a good stability. Surgical approach with percutaneous indirect articular reduction by elevating,minimal osteosynthesis and the use of NORIAN Skeletal Repair System lets us reach three fundamental objectives stated before. NORIAN S.R.S, used to fill the bone gap resulting from the traumatic collapse of the metaphyseal bone, with its mechanical strength allows the stabilization of the joint fragments, the reduction and the relative ostheosyntesis, thus greatly shortening the functional recovery time. Methods: We reviewed 70 patients affected by tibial plateau fractures, treated with this percutaneous technique using the mineral bone substitute 56 fractures were uni-condylar, 21 type 41-B2 and 35 type 41-B3 (according to AO/OTA classificaction); 14 fractures were bicondylar (AO/OTA 41-C3). The minimum follow-up was 1 year. We used for clinical evaluation the Hohl assessment form, for the radiographs the criteria of Rasmussen. X-rays. Results: The final conclusions, resulting from integrated analysis of the clinical data and X-ray data, can be simplified and represented as follows: 52 cases could be considered excellent-good (74%), 14 fair (20%), and 4 poor (6%). Conclusions: We can claim that the recostruction of the tibial plateau by minimal invasive surgery such as the percutaneous indirect reduction by elevating minimal osteosyintesis and mechanical stability assured by NORIAN SRS, is a good improvement in order to cut-down the functional recovery time. Mobilization is allowed the day after surgery and weight-bearing within the first week in B2 e B3 fracture type and within four weeks in C3 type reducing to the minimum knee posthraumatic stiffness


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 8 - 8
1 Mar 2009
Betti E Vitale M Vaglini M
Full Access

The choice of the treatment of tibial plateau fractures remains a controversial topic in current traumatology practice. The best treatment must have three fundamental requirements: to be less invasive as possible, to result in a good reduction, to have a good stability. Surgical approach with percutaneous indirect articular reduction by elevating,minimal osteosynthesis and the use of NORIAN Skeletal Repair System lets us reach three fundamental objectives stated before. NORIAN S.R.S, used to fill the bone gap resulting from the traumatic collapse of the metaphyseal bone, with its mechanical strength allows the stabilization of the joint fragments, the reduction and the relative ostheosyntesis, thus greatly shortening the functional recovery time. We reviewed 70 patients affected by tibial plateau fractures, treated with this percutaneous technique using the mineral bone substitute Norian:. 56 fractures were unicondylar, 21 type 41-B2 and 35 type 41-B3 (according to AO/OTA classificaction); 14 fractures were bicondylar (AO/OTA 41-C3). The minimum follow-up was 1 year. We used for clinical evaluation the Hohl assessment form, for the radiographs the criteria of Rasmussen. X-rays. The final conclusions, resulting from integrated analysis of the clinical data and X-ray data, can be simplified and represented as follows: 52 cases could be considered excellent-good (74%), 14 fair (20%), and 4 poor (6%). We can claim that the recostruction of the tibial plateau by minimal invasive surgery such as the percutaneous indirect reduction by elevating minimal osteosyintesis and mechanical stability assured by NORIAN SRS, is a good improvement in order to cutdown the functional recovery time. Mobilization is allowed the day after surgery and weight-bearing within the first week in B2 e B3 fracture type and within four weeks in C3 type reducing to the minimum knee posthraumatic stiffness


Bone & Joint Research
Vol. 10, Issue 12 | Pages 844 - 845
8 Dec 2021
Chen H Chen L


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 174 - 174
1 Mar 2006
Betti E Morescalchi G
Full Access

The treatment of the complex tibial plateau fractures is often hard because in these fractures, the entity of the articular damage is always important, the reduction is not easy it entails often extensive exposure and the collapse of the metaphyseal bone, located beneath the reconstructed articular surface, makes the osteosynthesis mechanically unsafe for ten or twelve weeks. The percutaneus surgical treatment, let us reach three fundamental objectives: to be mini-invasive, to result in a good reduction, to have a stable fixation. Through a small skin incision at the metaphysis, a leever was inserted across a small door made on the cortical metaphiseal bone and the articular fragments were elevated and held in the reduced position. Temporarily the fragments were fixed with a Kirshner-wire and definitely fixed with one or more canulated screw NORIAN S.R.S, used to fill the bone gap resulted from the traumatic collapse of the metaphyseal bone, with its initial mechanical strenghth allows to stabilize the joint fragments reduction and the relative ostheosyntesis, thus shortening the functional recovery time. Since 1997 we operated 52 patients affected by tibial plateau fractures using this percutaneus technique with the application of the mineral bone substitute Norian. 42 fractures were unicondylar: 16 type B2 and 26 Type B3 according to AO classificaction; 10 fractures were bicondylar 4 type C2 and 6 type C3 AO classificaction. The minimum follow-up was 1 year. We used for clinical evaluation the Hohl assessment form, for the radiographs the criteria of Rasmussen X-rays. The final conclusions, resulting from integrated analysis of the clinical data and X-rays data, can be simplified and represented as follows: 26 cases can be considered excellent that is (50%), 12 good (23%), 10 fair (20%), and 4 poor (7%). In conclusion we can say that Norian offers a real advantage in displaced tibial plateau fractures, because it is an unlimited supply of bone substitute, an optimal filling for the irregular defects of the cancellous bone and because it gives an immediate mechanical support to the joint, integrating the percutaneous ostheosynthesis perfectly. It is an important improvement in order to cut down the functional recovery time with great benefit for patients


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_II | Pages 173 - 173
1 Apr 2005
Betti E Morescalchi G
Full Access

The treatment of complex tibial plateau fractures is often difficult because in these fractures the nature of the articular damage is always important, the reduction is not easy, often entailing extensive exposure, and the collapse of the metaphyseal bone, located beneath the reconstructed articular surface, makes the osteosynthesis mechanically unsafe for 10 or 12 weeks. There are three fundamental objectives of percutaneous surgical treatment: to be minimally invasive, to result in a good reduction and to achieve stable fixation. Through a small skin incision at the metaphysis, a leever was inserted across a small door made on the cortical metaphyseal bone and the articular fragments were elevated and held in the reduced position. Temporarily the fragments were fixed with a Kirschner wire and definitely fixed with one or more cannulated screws. Norian S.R.S was used to fill the bone gap that resulted from the traumatic collapse of the metaphyseal bone: with its initial mechanical strength the joint fragment reduction and the developing ostheosynthesis can be stabilised, thus shortening the functional recovery time. Between 1997 and 2002 we operated 52 patients with tibial plateau fractures using this percutaneous technique and application of the mineral bone substitute Norian. Of these, 42 fractures were unicondylar, 16 type B2 and 26 Type B3 according to the AO classification, and 10 fractures bicondylar 4 type C2 and 6 type C3 according to the AO classification. The minimum follow-up was 1 year. For clinical evaluation we used the Hohl assessment form, for the radiographs the criteria of Rasmussen X-rays. The final conclusions, resulting from integrated analysis of the clinical data and X-ray data, can be simplified and represented as follows: 26 cases can be considered excellent (50%), 12 good (23%), 11 fair (21 %) and three poor (6%). In conclusion, Norian offers a real advantage in the treatment of displaced tibial plateau fractures, because it offers an unlimited supply of bone substitute, is an optimal filling for the irregular defects of the cancellous bone and gives immediate mechanical support to the joint, integrating the ostheosynthesis perfectly. The recostruction of the tibial plateau with minimally invasive surgery such as percutaneous indirect reduction by elevation and percutaneous osteosynthesis, with mechanical stability assured by Norian SRS, is an important improvement. The functional recovery time is reduced, with great benefit for patients


Introduction. The prevalence of symptomatic osteoarthritis (OA) in the knee is 11–11% compared to 3.4–4.4% in the ankle. In addition to this, 70% of ankle arthritis is post-traumatic while the vast majority of knee arthritis is primary OA. Several reports have previously implicated biochemical differences in extracellular matrix composition between these joint cartilages; however, it is unknown whether there is an inherent difference in their transcriptome and how this might affect their respective functionality under load, inflammatory environment etc. Therefore, we have analysed the transcriptome of ankle and knee cartilage chondrocytes to determine whether this could account for the lower prevalence and altered aetiology of ankle OA. Methods. Human full-depth articular cartilage was taken from the talar domes (n=5) and the femoral condyles (n=5) following surgical amputation. RNA was extracted and next generation sequencing (NGS) performed using the NextSeq®500 system. Statistical analysis was performed to identify differentially regulated genes (p adj < 0.05). Data was analysed using Integrated Pathway Analysis software and genes of interest validated by quantitative PCR. Results. 809 genes were differentially expressed in this NGS study: 781 genes were significantly up-regulated and 27 significantly down-regulated in ankle cartilage with respect to knee. Preliminary analysis has identified several pathways which are differentially regulated including ‘inflammation mediated by cytokines’, ‘glutamate receptor pathway, ‘heterotrimeric-G-protein signalling pathways’, ‘WNT signalling’ and ‘integrin signalling’. Discussion. This is the first report identifying genes that are differentially expressed in ankle cartilage compared to the knee. Validation is currently being performed to ascertain the importance of these gene changes and correlation with their protein expression in the different joints. An understanding of the inherent biological differences in the cartilage between these two joints will provide invaluable insight into why the ankle is relatively spared from primary OA and the majority of ankle arthritis occurs following trauma


Bone & Joint Research
Vol. 7, Issue 4 | Pages 298 - 307
1 Apr 2018
Zhang X Bu Y Zhu B Zhao Q Lv Z Li B Liu J

Objectives

The aim of this study was to identify key pathological genes in osteoarthritis (OA).

Methods

We searched and downloaded mRNA expression data from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) of joint synovial tissues from OA and normal individuals. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses were used to assess the function of identified DEGs. The protein-protein interaction (PPI) network and transcriptional factors (TFs) regulatory network were used to further explore the function of identified DEGs. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the result of bioinformatics analysis. Electronic validation was performed to verify the expression of selected DEGs. The diagnosis value of identified DEGs was accessed by receiver operating characteristic (ROC) analysis.


Bone & Joint 360
Vol. 6, Issue 6 | Pages 38 - 40
1 Dec 2017