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Bone & Joint Research
Vol. 3, Issue 3 | Pages 82 - 88
1 Mar 2014
Abdel MP Morrey ME Barlow JD Grill DE Kolbert CP An KN Steinmann SP Morrey BF Sanchez-Sotelo J

Objectives

The goal of this study was to determine whether intra-articular administration of the potentially anti-fibrotic agent decorin influences the expression of genes involved in the fibrotic cascade, and ultimately leads to less contracture, in an animal model.

Methods

A total of 18 rabbits underwent an operation on their right knees to form contractures. Six limbs in group 1 received four intra-articular injections of decorin; six limbs in group 2 received four intra-articular injections of bovine serum albumin (BSA) over eight days; six limbs in group 3 received no injections. The contracted limbs of rabbits in group 1 were biomechanically and genetically compared with the contracted limbs of rabbits in groups 2 and 3, with the use of a calibrated joint measuring device and custom microarray, respectively.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 62 - 62
1 Jul 2014
Abdel M Morrey M Barlowv J Grill D Kolbert C An K Steinmann S Morrey B Sanchez-Sotelo J
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Summary

Based upon genetic analysis, decorin is an exciting pharmacologic agent of potential anti-fibrogenic effect on arthrofibrosis in our animal model.

Introduction

While the pathophysiology of arthrofibrosis is not fully understood, some anti-fibrotic molecules such as decorin could potentially be used for the prevention or treatment of joint stiffness. The goal of this study was to determine whether intra-articular administration of decorin influences the expression of genes involved in the fibrotic cascade ultimately leading to less contracture in an animal model.


Bone & Joint Research
Vol. 5, Issue 1 | Pages 11 - 17
1 Jan 2016
Barlow JD Morrey ME Hartzler RU Arsoy D Riester S van Wijnen AJ Morrey BF Sanchez-Sotelo J Abdel MP

Aims. Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone. Methods. A total of 20 rabbits underwent contracture-forming surgery. Eight weeks later, the animals underwent a surgical capsular release. Ten animals received rosiglitazone (intramuscular initially, then orally). The animals were sacrificed following 16 weeks of free cage mobilisation. The joints were tested biomechanically, and the posterior capsule was assessed histologically and via genetic microarray analysis. Results. There was no significant difference in post-traumatic contracture between the rosiglitazone and control groups (33° (standard deviation (. sd. ) 11) vs 37° (. sd. 14), respectively; p = 0.4). There was no difference in number or percentage of myofibroblasts. Importantly, there were ten genes and 17 pathways that were significantly modulated by rosiglitazone in the posterior capsule. Discussion. Rosiglitazone significantly altered the genetic expression of the posterior capsular tissue in a rabbit model, with ten genes and 17 pathways demonstrating significant modulation. However, there was no significant effect on biomechanical or histological properties. Cite this article: M. P. Abdel. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis. Bone Joint Res 2016;5:11–17. doi: 10.1302/2046-3758.51.2000593


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 447 - 447
1 Dec 2013
Nakanishi Y Hidehiko H Miura H Shiraishi Y Shimoto T Umeno T Mizuta H Iwamoto Y
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An ultra-high molecular weight polyethylene (UHMWPE) is widely used as bearing material in artificial joints, however, UHMWPE wear particles are considered to be a major factor in long-term osteolysis and loosening of implants. The wear particles activate macrophages, which release cytokines, stimulating osteoclasts, which results in bone resorption. The biological activity of the wear debris is dependent on the volume and size of the particles produced. Many researchers reported that the volume and size of particles were critical factors in macrophage activation, which particles in the size range of 0.1–1 mm being the most biological active. To minimize the amount of wear of UHMWPE and to enlarge the size of UHMWPE wear particle, a nano-level surface textured on Co-Cr-Mo alloy as a counterface material was invented (Figure 1). Although the generally-used surface for a conventional artificial joint has 10 nm roughness (G-1), the nano-level surface has a superfine surface of 1 nm with groove and dimples against the bearing area. The existence probability of groove or dimples, and their surface waviness were adjusted (P-1, 2, 3, 4 and W-1, 2). Pin-on-disc wear tester capable of multidirectional motions was used to verify that the nano-textured surface is the most appropriate for artificial joint. UHMWPE pin with an average molecular weight of 6.0 million was placed in contact with the disc and the contact pressure was 6.0 MPa. The disc and pin were lubricated by a water-based liquid containing the principal constituents of natural synovial fluid. Sliding speed of 12.12 mm/s had been applied for total sliding distance of 15 km. The nano-textured surfaces reduced the amount of UHMWPE wear, this would ensure the long-term durability of artificial joint (Figure 2). The wear particles isolated from lubricating liquid were divided broadly into two categories; one is “simple type” and the other is “complicated type”. The lengths in a longitudinal direction (Ll) and its orthogonal direction (Ls) for each particles (>150) were measured, and the each aspect ratio (= Ll/Ls) was calculated. No significant difference was found in the ratio between simple type and complicated type, and in the distributions of aspect ratios. However, the distributions of Ll, which means the size of UHMWPE wear particle, were dramatically changed by using the nano-textured surface (Figure 3). These results suggest that the nano-textured surface does not change the morphological aspect of UHMWPE particle but enlarges the size of UHMWPE particle. Cells (RAW264.7, blood, Mouse) were cultured with the particles in supplemented Dulbecco's modified Eagle's medium for 24 h in an atmosphere of 5% CO. 2. in air at 37 degrees C, and the quantitative PCR was performed for genetic expression of IL-6. The wear debris generated on the nano-textured surface inhibited the genetic expression of IL-6, which does not induce the tissue reaction and joint loosening


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_15 | Pages 278 - 278
1 Mar 2013
Nakanishi Y Miura H Tokunaga K Hidehiko H Mizuta H Iwamoto Y
Full Access

An ultra-high molecular weight polyethylene (UHMWPE) is widely used as bearing material in artificial joints, however, UHMWPE wear particles are considered to be a major factor in long-term osteolysis and loosening of implants. The wear particles activate macrophages, which release cytokines, stimulating osteoclasts, which results in bone resorption. The biological activity of the wear debris is dependent on the volume and size of the particles produced. Many researchers reported that the volume and size of particles were critical factors in macrophage activation, which particles in the size range of 0.1–1 mm being the most biological active. To minimize the amount of wear of UHMWPE and to enlarge the size of UHMWPE wear particle, a nano-level surface texturing on Co-Cr-Mo alloy as a counterface material was invented. Although the generally-used surface for a conventional artificial joint has 10 nm roughness (Surface A), the nano-level textured surface invented has a superfine surface of 1 nm with 3% of groove and dimples against the bearing area. The depths of groove and dimples are less than 50 nm (Surface F). Pin-on-disc wear tester capable of multidirectional motions was used to verify that the nano-textured surface is the most appropriate for artificial joint. UHMWPE pin with an average molecular weight of 6.0 million was placed in contact with the disc and the contact pressure was 6.0 MPa. The disc and pin were lubricated by a water-based liquid containing the principal constituents of natural synovial fluid. Sliding speed of 12.12 mm/s had been applied for total sliding distance of 15 km. The superfine surface with nano-level grooves and dimples (Surface F) reduced the amount of UHMWPE wear, this would ensure the long-term durability of artificial joint. The wear particles isolated from lubricating liquid were divided broadly into two categories; one is “simple type” and the other is “complicated type”. The lengths in a longitudinal direction (Ll) and its orthogonal direction (Ls) for each particles (>150) were measured, and the each aspect ratio (= Ll/Ls) was calculated. No significant difference was found in the ratio between simple type and complicated type, and in the distributions of aspect ratios. However, the distributions of Ll, which means the size of UHMWPE wear particle, were dramatically changed by using the nano-textured surface (Figure 2). These results suggest that the nano-textured surface does not change the morphological aspect of UHMWPE particle but enlarges the size of UHMWPE particle. Cells (RAW264.7, blood, Mouse) were cultured with the particles in supplemented Dulbecco's modified Eagle's medium for 24 h in an atmosphere of 5% CO. 2. in air at 37 degrees C, and the quantitative PCR was performed for genetic expression of IL-6 (Figure 3). The wear debris generated on the nano-textured surface inhibited the genetic expression of IL-6, which does not induce the tissue reaction and joint loosening


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 245 - 245
1 Jul 2011
Maragh K Bater J Secretan C Bagnall KM Jomha NM
Full Access

Purpose: Current techniques for articular cartilage repair remain suboptimal. The best technique involves the introduction of cultured chondrocytes into the injury site. Experimental results of current chondrocyte culture and expansion techniques (passaging) have shown phenotypic alteration resulting in fibroblast-like cells. Therefore, treatment methods that propose the transplantation of cultured chondrocytes might be transplanting fibroblast-like cells instead of chondrocytes. This experiment explored the difference in genetic expression of chondrocytes left at confluence compared to chondrocytes that were passaged as performed in current culture techniques. It was hypothesized that chondrocytes left at confluence would maintain their collagen I and collagen II gene expression over time. Method: Fresh normal human articular cartilage was collected from deceased donor patients. The matrix was digested and the chondrocytes were plated in monolayer to create two groups. The first group was cultured and passaged 2? at confluence seven times. The second group was cultured at confluence and left for seven weeks, with medium changes every 3–4 days without passaging. At weekly intervals RNA was extracted from cells in both groups and analyzed with real time PCR, probing specifically for the genes responsible for the production of collagen I, collagen II, aggrecan, and GAPDH. This was done in duplicate. Results: Collagen II gene expression was maintained over seven weeks in cells left at confluence but was decreased in passaged cells. Collagen I gene expression decreased over seven weeks in cells left at confluence, but remained the same in passaged cells. Aggrecan gene expression remained the same in both groups. Conclusion: Current culture and expansion techniques that employ passaging (as used in clinical scenarios) result in significant alterations in gene expression that are inconsistent with the current definition of a “chondrocyte”. Culturing chondrocytes at confluence can produce gene expression more similar to native chondrocytes but even these cells have expression of collagen type I that should not be present in chondrocytes. The results of this study suggest that further investigation is required to develop chondrocyte culture and expansion techniques that minimize the de-differentiation of chondrocytes by maintaining collagen II gene expression and eliminating/preventing collagen I gene expression


The Bone & Joint Journal
Vol. 105-B, Issue 2 | Pages 198 - 208
1 Feb 2023
Cheok T Smith T Wills K Jennings MP Rawat J Foster B

Aims

We investigated the prevalence of late developmental dysplasia of the hip (DDH), abduction bracing treatment, and surgical procedures performed following the implementation of universal ultrasound screening versus selective ultrasound screening programmes.

Methods

A systematic search of PubMed, Embase, The Cochrane Library, OrthoSearch, and Web of Science from the date of inception of each database until 27 March 2022 was performed. The primary outcome of interest was the prevalence of late detection of DDH, diagnosed after three months. Secondary outcomes of interest were the prevalence of abduction bracing treatment and surgical procedures performed in childhood for dysplasia. Only studies describing the primary outcome of interest were included.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 522 - 535
4 Sep 2023
Zhang G Li L Luo Z Zhang C Wang Y Kang X

Aims

This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

Methods

The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.


Bone & Joint Research
Vol. 9, Issue 1 | Pages 36 - 48
1 Jan 2020
González-Chávez SA Pacheco-Tena C Quiñonez-Flores CM Espino-Solis GP Burrola-De Anda JI Muñoz-Morales PM

Aims

To assess the effect of physical exercise (PE) on the histological and transcriptional characteristics of proteoglycan-induced arthritis (PGIA) in BALB/c mice.

Methods

Following PGIA, mice were subjected to treadmill PE for ten weeks. The tarsal joints were used for histological and genetic analysis through microarray technology. The genes differentially expressed by PE in the arthritic mice were obtained from the microarray experiments. Bioinformatic analysis in the DAVID, STRING, and Cytoscape bioinformatic resources allowed the association of these genes in biological processes and signalling pathways.


Bone & Joint 360
Vol. 2, Issue 6 | Pages 2 - 8
1 Dec 2013
Jones R Wood D

This article provides an overview of the role of genomics in sarcomas and describes how new methods of analysis and comparative screening have provided the potential to progress understanding and treatment of sarcoma. This article reviews genomic techniques, the evolution of the use of genomics in cancer, the current state of genomic analysis, and also provides an overview of the medical, social and economic implications of recent genomic advances.