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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.


The Bone & Joint Journal
Vol. 101-B, Issue 7 | Pages 824 - 831
1 Jul 2019
Mahmoud EE Adachi N Mawas AS Deie M Ochi M

Aim

Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model.

Materials and Methods

Two months after bilateral section of the ACL of Japanese white rabbits aged nine months or more, either phosphate buffered saline (PBS) or 1 x 106 MSCs were injected into the knee joint in single or three consecutive doses. After two months, the articular cartilage and meniscus were assessed macroscopically, histologically, and immunohistochemically using collagen I and II.


Objectives

Adult mice lacking the transcription factor NFAT1 exhibit osteoarthritis (OA). The precise molecular mechanism for NFAT1 deficiency-induced osteoarthritic cartilage degradation remains to be clarified. This study aimed to investigate if NFAT1 protects articular cartilage (AC) against OA by directly regulating the transcription of specific catabolic and anabolic genes in articular chondrocytes.

Methods

Through a combined approach of gene expression analysis and web-based searching of NFAT1 binding sequences, 25 candidate target genes that displayed aberrant expression in Nfat1-/- AC at the initiation stage of OA, and possessed at least four NFAT1 binding sites in the promoter of each gene, were selected and tested for NFAT1 transcriptional activities by chromatin immunoprecipitation (ChIP) and promoter luciferase reporter assays using chondrocytes isolated from the AC of three- to four-month-old wild-type mice or Nfat1-/- mice with early OA phenotype.


Bone & Joint Research
Vol. 9, Issue 8 | Pages 501 - 514
1 Aug 2020
Li X Yang Y Sun G Dai W Jie X Du Y Huang R Zhang J

Aims

Rheumatoid arthritis (RA) is a systematic autoimmune disorder, characterized by synovial inflammation, bone and cartilage destruction, and disease involvement in multiple organs. Although numerous drugs are employed in RA treatment, some respond little and suffer from severe side effects. This study aimed to screen the candidate therapeutic targets and promising drugs in a novel method.

Methods

We developed a module-based and cumulatively scoring approach that is a deeper-layer application of weighted gene co-expression network (WGCNA) and connectivity map (CMap) based on the high-throughput datasets.


Bone & Joint Research
Vol. 8, Issue 6 | Pages 232 - 245
1 Jun 2019
Lu C Zhang T Reisdorf RL Amadio PC An K Moran SL Gingery A Zhao C

Objectives

Re-rupture is common after primary flexor tendon repair. Characterization of the biological changes in the ruptured tendon stumps would be helpful, not only to understand the biological responses to the failed tendon repair, but also to investigate if the tendon stumps could be used as a recycling biomaterial for tendon regeneration in the secondary grafting surgery.

Methods

A canine flexor tendon repair and failure model was used. Following six weeks of repair failure, the tendon stumps were analyzed and characterized as isolated tendon-derived stem cells (TDSCs).


The Bone & Joint Journal
Vol. 102-B, Issue 3 | Pages 336 - 344
1 Mar 2020
Ji B Li G Zhang X Wang Y Mu W Cao L

Aims

In the absence of an identified organism, single-stage revision is contraindicated in prosthetic joint infection (PJI). However, no studies have examined the use of intra-articular antibiotics in combination with single-stage revision in these cases. In this study, we present the results of single-stage revision using intra-articular antibiotic infusion for treating culture-negative (CN) PJI.

Methods

A retrospective analysis between 2009 and 2016 included 51 patients with CN PJI who underwent single-stage revision using intra-articular antibiotic infusion; these were compared with 192 culture-positive (CP) patients. CN patients were treated according to a protocol including intravenous vancomycin and a direct intra-articular infusion of imipenem and vancomycin alternately used in the morning and afternoon. In the CP patients, pathogen-sensitive intravenous (IV) antibiotics were administered for a mean of 16 days (12 to 21), and for resistant cases, additional intra-articular antibiotics were used. The infection healing rate, Harris Hip Score (HHS), and Hospital for Special Surgery (HSS) knee score were compared between CN and CP groups.


Bone & Joint Research
Vol. 9, Issue 3 | Pages 130 - 138
1 Mar 2020
Qi X Yu F Wen Y Li P Cheng B Ma M Cheng S Zhang L Liang C Liu L Zhang F

Aims

Osteoarthritis (OA) is the most prevalent joint disease. However, the specific and definitive genetic mechanisms of OA are still unclear.

Methods

Tissue-related transcriptome-wide association studies (TWAS) of hip OA and knee OA were performed utilizing the genome-wide association study (GWAS) data of hip OA and knee OA (including 2,396 hospital-diagnosed hip OA patients versus 9,593 controls, and 4,462 hospital-diagnosed knee OA patients versus 17,885 controls) and gene expression reference to skeletal muscle and blood. The OA-associated genes identified by TWAS were further compared with the differentially expressed genes detected by the messenger RNA (mRNA) expression profiles of hip OA and knee OA. Functional enrichment and annotation analysis of identified genes was performed by the DAVID and FUMAGWAS tools.


Bone & Joint Research
Vol. 7, Issue 5 | Pages 373 - 378
1 May 2018
Johnson-Lynn SE McCaskie AW Coll AP Robinson AHN

Charcot neuroarthropathy is a rare but serious complication of diabetes, causing progressive destruction of the bones and joints of the foot leading to deformity, altered biomechanics and an increased risk of ulceration.

Management is complicated by a lack of consensus on diagnostic criteria and an incomplete understanding of the pathogenesis. In this review, we consider recent insights into the development of Charcot neuroarthropathy.

It is likely to be dependent on several interrelated factors which may include a genetic pre-disposition in combination with diabetic neuropathy. This leads to decreased neuropeptides (nitric oxide and calcitonin gene-related peptide), which may affect the normal coupling of bone formation and resorption, and increased levels of Receptor activator of nuclear factor kappa-B ligand, potentiating osteoclastogenesis.

Repetitive unrecognized trauma due to neuropathy increases levels of pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumour necrosis factor α) which could also contribute to increased bone resorption, in combination with a pre-inflammatory state, with increased autoimmune reactivity and a profile of monocytes primed to transform into osteoclasts - cluster of differentiation 14 (CD14).

Increased blood glucose and loss of circulating Receptor for Advanced Glycation End-Products (AGLEPs), leading to increased non-enzymatic glycation of collagen and accumulation of AGLEPs in the tissues of the foot, may also contribute to the pathological process.

An understanding of the relative contributions of each of these mechanisms and a final common pathway for the development of Charcot neuroarthropathy are still lacking.

Cite this article: S. E. Johnson-Lynn, A. W. McCaskie, A. P. Coll, A. H. N. Robinson. Neuroarthropathy in diabetes: pathogenesis of Charcot arthropathy. Bone Joint Res 2018;7:373–378. DOI: 10.1302/2046-3758.75.BJR-2017-0334.R1.


Bone & Joint Research
Vol. 8, Issue 7 | Pages 290 - 303
1 Jul 2019
Li H Yang HH Sun ZG Tang HB Min JK

Objectives

The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA).

Methods

The expression profiles of mRNAs, lncRNAs, and circRNAs in OA cartilage were assessed using whole-transcriptome sequencing. Bioinformatics analyses included prediction and reannotation of novel lncRNAs and circRNAs, their classification, and their placement into subgroups. Gene ontology and pathway analysis were performed to identify differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs). We focused on the overlap of DEGs and targets of DELs previously identified in seven high-throughput studies. The top ten DELs were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in articular chondrocytes, both in vitro and in vivo.


Bone & Joint Research
Vol. 7, Issue 3 | Pages 252 - 262
1 Mar 2018
Nishida K Matsushita T Takayama K Tanaka T Miyaji N Ibaraki K Araki D Kanzaki N Matsumoto T Kuroda R

Objectives

This study aimed to examine the effects of SRT1720, a potent SIRT1 activator, on osteoarthritis (OA) progression using an experimental OA model.

Methods

Osteoarthritis was surgically induced by destabilization of the medial meniscus in eight-week-old C57BL/6 male mice. SRT1720 was administered intraperitoneally twice a week after surgery. Osteoarthritis progression was evaluated histologically using the Osteoarthritis Research Society International (OARSI) score at four, eight, 12 and 16 weeks. The expression of SIRT1, matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), cleaved caspase-3, PARP p85, and acetylated nuclear factor (NF)-κB p65 in cartilage was examined by immunohistochemistry. Synovitis was also evaluated histologically. Primary mouse epiphyseal chondrocytes were treated with SRT1720 in the presence or absence of interleukin 1 beta (IL-1β), and gene expression changes were examined by real-time polymerase chain reaction (PCR).


The Bone & Joint Journal
Vol. 100-B, Issue 7 | Pages 984 - 988
1 Jul 2018
Gortzak Y Vitenberg M Frenkel Rutenberg T Kollender Y Dadia S Sternheim A Morag G Farkash U Rath E Kramer M Drexler M

Aims

Intra-articular 90Yttrium (90Y) is an adjunct to surgical treatment by synovectomy for patients with diffuse-type tenosynovial giant-cell tumour (dtTGCT) of the knee, with variable success rates. Clinical information is, however, sparse and its value remains unclear. We investigated the long-term outcome of patients who underwent synovectomy with and without adjuvant treatment with 90Yttrium.

Patients and Methods

All patients with dtTGCT of the knee who underwent synovectomy between 1991 and 2014 were included in the study. Group A patients underwent synovectomy and an intra-articular injection of 90Yttrium between six and eight weeks after surgery. Group B patients underwent surgery alone.


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 Research
Vol. 8, Issue 12 | Pages 582 - 592
1 Dec 2019
Sansone V Applefield RC De Luca P Pecoraro V Gianola S Pascale W Pascale V

Aims

The aim of this study was to systematically review the literature for evidence of the effect of a high-fat diet (HFD) on the onset or progression of osteoarthritis (OA) in mice.

Methods

A literature search was performed in PubMed, Embase, Web of Science, and Scopus to find all studies on mice investigating the effects of HFD or Western-type diet on OA when compared with a control diet (CD). The primary outcome was the determination of cartilage loss and alteration. Secondary outcomes regarding local and systemic levels of proteins involved in inflammatory processes or cartilage metabolism were also examined when reported.


The Bone & Joint Journal
Vol. 101-B, Issue 10 | Pages 1238 - 1247
1 Oct 2019
Soreide E Denbeigh JM Lewallen EA Thaler R Xu W Berglund L Yao JJ Martinez A Nordsletten L van Wijnen AJ Kakar S

Aims

Options for the treatment of intra-articular ligament injuries are limited, and insufficient ligament reconstruction can cause painful joint instability, loss of function, and progressive development of degenerative arthritis. This study aimed to assess the capability of a biologically enhanced matrix material for ligament reconstruction to withstand tensile forces within the joint and enhance ligament regeneration needed to regain joint function.

Materials and Methods

A total of 18 New Zealand rabbits underwent bilateral anterior cruciate ligament reconstruction by autograft, FiberTape, or FiberTape-augmented autograft. Primary outcomes were biomechanical assessment (n = 17), microCT (µCT) assessment (n = 12), histological evaluation (n = 12), and quantitative polymerase chain reaction (qPCR) analysis (n = 6).


Bone & Joint 360
Vol. 8, Issue 4 | Pages 5 - 13
1 Aug 2019
Middleton R Khan T Alvand A


The Bone & Joint Journal
Vol. 100-B, Issue 7 | Pages 898 - 902
1 Jul 2018
Lachiewicz PF O’Dell JA

Aims

To report our experience with trunnion corrosion following metal-on-polyethylene total hip arthroplasty, in particular to report the spectrum of presentation and determine the mean time to presentation.

Patients and Methods

We report the presenting symptoms and signs, intraoperative findings, and early results and complications of operative treatment in nine patients with a mean age of 74 years (60 to 86). The onset of symptoms was at a mean of seven years (3 to 18) after index surgery.


Bone & Joint 360
Vol. 8, Issue 2 | Pages 16 - 18
1 Apr 2019


The Bone & Joint Journal
Vol. 101-B, Issue 4 | Pages 396 - 402
1 Apr 2019
Ji B Wahafu T Li G Zhang X Wang Y Momin M Cao L

Aims

Single-stage revision is not widely pursued due to restrictive inclusion criteria. In this study, we evaluated the results of single-stage revision of chronically infected total hip arthroplasty (THA) using broad inclusion criteria and cementless implants.

Patients and Methods

Between 2010 and 2016, 126 patients underwent routine single-stage revision with cementless reconstruction with powdered vancomycin or imipenem poured into the medullary cavity and re-implantation of cementless components. For patients with a culture-negative hip, fungal infections, and multidrug-resistant organisms, a direct intra-articular infusion of pathogen-sensitive antibiotics was performed postoperatively. Recurrence of infection and clinical outcomes were evaluated. Three patients died and 12 patients (none with known recurrent infection) were lost to follow-up. There were 111 remaining patients (60 male, 51 female) with a mean age of 58.7 (sd 12.7; 20 to 79).


Bone & Joint Research
Vol. 7, Issue 4 | Pages 274 - 281
1 Apr 2018
Collins KH Hart DA Seerattan RA Reimer RA Herzog W

Objectives

Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes.

Methods

A total of 16 male Sprague-Dawley rats were allocated to either the diet-induced obesity group (DIO, 40% fat, 45% sucrose, n = 9) or a chow control diet (n = 7) for 12 weeks. At sacrifice, histological assessments of the shoulder, hip, and knee joints were performed. Serum inflammatory mediators and body composition were also evaluated. The total Mankin score for each animal was assessed by adding together the individual Modified Mankin scores across all three joints. Linear regression modelling was conducted to evaluate predictive relationships between serum mediators and total joint damage.


Bone & Joint Research
Vol. 7, Issue 11 | Pages 587 - 594
1 Nov 2018
Zhang R Li G Zeng C Lin C Huang L Huang G Zhao C Feng S Fang H

Objectives

The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known.

Methods

In this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours.