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Bone & Joint Research
Vol. 13, Issue 2 | Pages 66 - 82
5 Feb 2024
Zhao D Zeng L Liang G Luo M Pan J Dou Y Lin F Huang H Yang W Liu J

Aims. This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Methods. Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization. Results. A total of 46 genes were obtained from the intersection of significantly upregulated genes in osteoarthritic cartilage and the key module genes screened by WGCNA. Functional annotation analysis revealed that these genes were closely related to pathological responses associated with OA, such as inflammation and immunity. Four key dysregulated genes (cartilage acidic protein 1 (CRTAC1), iodothyronine deiodinase 2 (DIO2), angiopoietin-related protein 2 (ANGPTL2), and MAGE family member D1 (MAGED1)) were identified after using machine-learning algorithms. These genes had high diagnostic value in both the training cohort and external validation cohort (receiver operating characteristic > 0.8). The upregulated expression of these hub genes in osteoarthritic cartilage signified higher levels of immune infiltration as well as the expression of metalloproteinases and mineralization markers, suggesting harmful biological alterations and indicating that these hub genes play an important role in the pathogenesis of OA. A competing endogenous RNA network was constructed to reveal the underlying post-transcriptional regulatory mechanisms. Conclusion. The current study explores and validates a dysregulated key gene set in osteoarthritic cartilage that is capable of accurately diagnosing OA and characterizing the biological alterations in osteoarthritic cartilage; this may become a promising indicator in clinical decision-making. This study indicates that dysregulated key genes play an important role in the development and progression of OA, and may be potential therapeutic targets. Cite this article: Bone Joint Res 2024;13(2):66–82


Bone & Joint Open
Vol. 2, Issue 1 | Pages 48 - 57
19 Jan 2021
Asokan A Plastow R Kayani B Radhakrishnan GT Magan AA Haddad FS

Cementless knee arthroplasty has seen a recent resurgence in popularity due to conceptual advantages, including improved osseointegration providing biological fixation, increased surgical efficiency, and reduced systemic complications associated with cement impaction and wear from cement debris. Increasingly younger and higher demand patients are requiring knee arthroplasty, and as such, there is optimism cementless fixation may improve implant survivorship and functional outcomes. Compared to cemented implants, the National Joint Registry (NJR) currently reports higher revision rates in cementless total knee arthroplasty (TKA), but lower in unicompartmental knee arthroplasty (UKA). However, recent studies are beginning to show excellent outcomes with cementless implants, particularly with UKA which has shown superior performance to cemented varieties. Cementless TKA has yet to show long-term benefit, and currently performs equivalently to cemented in short- to medium-term cohort studies. However, with novel concepts including 3D-printed coatings, robotic-assisted surgery, radiostereometric analysis, and kinematic or functional knee alignment principles, it is hoped they may help improve the outcomes of cementless TKA in the long-term. In addition, though cementless implant costs remain higher due to novel implant coatings, it is speculated cost-effectiveness can be achieved through greater surgical efficiency and potential reduction in revision costs. There is paucity of level one data on long-term outcomes between fixation methods and the cost-effectiveness of modern cementless knee arthroplasty. This review explores recent literature on cementless knee arthroplasty, with regards to clinical outcomes, implant survivorship, complications, and cost-effectiveness; providing a concise update to assist clinicians on implant choice. Cite this article: Bone Jt Open 2021;2(1):48–57


Bone & Joint Open
Vol. 5, Issue 5 | Pages 401 - 410
20 May 2024
Bayoumi T Burger JA van der List JP Sierevelt IN Spekenbrink-Spooren A Pearle AD Kerkhoffs GMMJ Zuiderbaan HA

Aims

The primary objective of this registry-based study was to compare patient-reported outcomes of cementless and cemented medial unicompartmental knee arthroplasty (UKA) during the first postoperative year. The secondary objective was to assess one- and three-year implant survival of both fixation techniques.

Methods

We analyzed 10,862 cementless and 7,917 cemented UKA cases enrolled in the Dutch Arthroplasty Registry, operated between 2017 and 2021. Pre- to postoperative change in outcomes at six and 12 months’ follow-up were compared using mixed model analyses. Kaplan-Meier and Cox regression models were applied to quantify differences in implant survival. Adjustments were made for patient-specific variables and annual hospital volume.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 58 - 71
17 Jan 2023
Dagneaux L Limberg AK Owen AR Bettencourt JW Dudakovic A Bayram B Gades NM Sanchez-Sotelo J Berry DJ van Wijnen A Morrey ME Abdel MP

Aims

As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA).

Methods

Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 342 - 352
9 Jul 2024
Cheng J Jhan S Chen P Hsu S Wang C Moya D Wu Y Huang C Chou W Wu K

Aims

To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration.

Methods

The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm2, 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens.


Bone & Joint Open
Vol. 3, Issue 2 | Pages 107 - 113
1 Feb 2022
Brunt ACC Gillespie M Holland G Brenkel I Walmsley P

Aims

Periprosthetic joint infection (PJI) occurs in approximately 1% to 2% of total knee arthroplasties (TKA) presenting multiple challenges, such as difficulty in diagnosis, technical complexity, and financial costs. Two-stage exchange is the gold standard for treating PJI but emerging evidence suggests 'two-in-one' single-stage revision as an alternative, delivering comparable outcomes, reduced morbidity, and cost-effectiveness. This study investigates five-year results of modified single-stage revision for treatment of PJI following TKA with bone loss.

Methods

Patients were identified from prospective data on all TKA patients with PJI following the primary procedure. Inclusion criteria were: revision for PJI with bone loss requiring reconstruction, and a minimum five years’ follow-up. Patients were followed up for recurrent infection and assessment of function. Tools used to assess function were Oxford Knee Score (OKS) and American Knee Society Score (AKSS).


Bone & Joint Open
Vol. 2, Issue 8 | Pages 576 - 582
2 Aug 2021
Fuchs M Kirchhoff F Reichel H Perka C Faschingbauer M Gwinner C

Aims

Current guidelines consider analyses of joint aspirates, including leucocyte cell count (LC) and polymorphonuclear percentage (PMN%) as a diagnostic mainstay of periprosthetic joint infection (PJI). It is unclear if these parameters are subject to a certain degree of variability over time. Therefore, the aim of this study was to evaluate the variation of LC and PMN% in patients with aseptic revision total knee arthroplasty (TKA).

Methods

We conducted a prospective, double-centre study of 40 patients with 40 knee joints. Patients underwent joint aspiration at two different time points with a maximum period of 120 days in between these interventions and without any events such as other joint aspirations or surgeries. The main indications for TKA revision surgery were aseptic implant loosening (n = 24) and joint instability (n = 11).


Bone & Joint Open
Vol. 2, Issue 6 | Pages 414 - 421
1 Jun 2021
Kim SK Nguyen C Avins AL Abrams GD

Aims

The aim of this study was to screen the entire genome for genetic markers associated with risk for anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) injury.

Methods

Genome-wide association (GWA) analyses were performed using data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. ACL and PCL injury cases were identified based on electronic health records from KPRB and the UK Biobank. GWA analyses from both cohorts were tested for ACL and PCL injury using a logistic regression model adjusting for sex, height, weight, age at enrolment, and race/ethnicity using allele counts for single nucleotide polymorphisms (SNPs). The data from the two GWA studies were combined in a meta-analysis. Candidate genes previously reported to show an association with ACL injury in athletes were also tested for association from the meta-analysis data from the KPRB and the UK Biobank GWA studies.


Bone & Joint Research
Vol. 10, Issue 8 | Pages 467 - 473
2 Aug 2021
Rodríguez-Collell JR Mifsut D Ruiz-Sauri A Rodríguez-Pino L González-Soler EM Valverde-Navarro AA

Aims

The main objective of this study is to analyze the penetration of bone cement in four different full cementation techniques of the tibial tray.

Methods

In order to determine the best tibial tray cementation technique, we applied cement to 40 cryopreserved donor tibiae by four different techniques: 1) double-layer cementation of the tibial component and tibial bone with bone restrictor; 2) metallic cementation of the tibial component without bone restrictor; 3) bone cementation of the tibia with bone restrictor; and 4) superficial bone cementation of the tibia and metallic keel cementation of the tibial component without bone restrictor. We performed CT exams of all 40 subjects, and measured cement layer thickness at both levels of the resected surface of the epiphysis and the endomedular metaphyseal level.


Bone & Joint Research
Vol. 9, Issue 9 | Pages 543 - 553
1 Sep 2020
Bakirci E Tschan K May RD Ahmad SS Kleer B Gantenbein B

Aims

The anterior cruciate ligament (ACL) is known to have a poor wound healing capacity, whereas other ligaments outside of the knee joint capsule such as the medial collateral ligament (MCL) apparently heal more easily. Plasmin has been identified as a major component in the synovial fluid that varies among patients. The aim of this study was to test whether plasmin, a component of synovial fluid, could be a main factor responsible for the poor wound healing capacity of the ACL.

Methods

The effects of increasing concentrations of plasmin (0, 0.1, 1, 10, and 50 µg/ml) onto the wound closing speed (WCS) of primary ACL-derived ligamentocytes (ACL-LCs) were tested using wound scratch assay and time-lapse phase-contrast microscopy. Additionally, relative expression changes (quantitative PCR (qPCR)) of major LC-relevant genes and catabolic genes were investigated. The positive controls were 10% fetal calf serum (FCS) and platelet-derived growth factor (PDGF).


The Bone & Joint Journal
Vol. 102-B, Issue 10 | Pages 1331 - 1340
3 Oct 2020
Attard V Li CY Self A Mann DA Borthwick LA O’Connor P Deehan DJ Kalson NS

Aims

Stiffness is a common complication after total knee arthroplasty (TKA). Pathogenesis is not understood, treatment options are limited, and diagnosis is challenging. The aim of this study was to investigate if MRI can be used to visualize intra-articular scarring in patients with stiff, painful knee arthroplasties.

Methods

Well-functioning primary TKAs (n = 11), failed non-fibrotic TKAs (n = 5), and patients with a clinical diagnosis of fibrosis1 (n = 8) underwent an MRI scan with advanced metal suppression (Slice Encoding for Metal Artefact Correction, SEMAC) with gadolinium contrast. Fibrotic tissue (low intensity on T1 and T2, low-moderate post-contrast enhancement) was quantified (presence and tissue thickness) in six compartments: supra/infrapatella, medial/lateral gutters, and posterior medial/lateral.


The Bone & Joint Journal
Vol. 101-B, Issue 6 | Pages 652 - 659
1 Jun 2019
Abram SGF Beard DJ Price AJ

Aims

The aim of the British Association for Surgery of the Knee (BASK) Meniscal Consensus Project was to develop an evidence-based treatment guideline for patients with meniscal lesions of the knee.

Materials and Methods

A formal consensus process was undertaken applying nominal group, Delphi, and appropriateness methods. Consensus was first reached on the terminology relating to the definition, investigation, and classification of meniscal lesions. A series of simulated clinical scenarios was then created and the appropriateness of arthroscopic meniscal surgery or nonoperative treatment in each scenario was rated by the group. The process was informed throughout by the latest published, and previously unpublished, clinical and epidemiological evidence. Scenarios were then grouped together based upon the similarity of clinical features and ratings to form the guideline for treatment. Feedback on the draft guideline was sought from the entire membership of BASK before final revisions and approval by the consensus group.


Bone & Joint Research
Vol. 5, Issue 6 | Pages 247 - 252
1 Jun 2016
Tabuchi K Soejima T Murakami H Noguchi K Shiba N Nagata K

Objectives

The objective of this study was to determine if the use of fascia lata as a tendon regeneration guide (placed into the tendon canal following harvesting the semitendinosus tendon) would improve the incidence of tissue regeneration and prevent fatty degeneration of the semitendinosus muscle.

Materials and Methods

Bilateral semitendinosus tendons were harvested from rabbits using a tendon stripper. On the inducing graft (IG) side, the tendon canal and semitendinosus tibial attachment site were connected by the fascia lata, which was harvested at the same width as the semitendinosus tendon. On the control side, no special procedures were performed. Two groups of six rabbits were killed at post-operative weeks 4 and 8, respectively. In addition, three healthy rabbits were killed to obtain normal tissue. We evaluated the incidence of tendon tissue regeneration, cross-sectional area of the regenerated tendon tissue and proportion of fatty tissue in the semitendinosus muscle.


Bone & Joint Research
Vol. 3, Issue 2 | Pages 20 - 31
1 Feb 2014
Kiapour AM Murray MM

Injury to the anterior cruciate ligament (ACL) is one of the most devastating and frequent injuries of the knee. Surgical reconstruction is the current standard of care for treatment of ACL injuries in active patients. The widespread adoption of ACL reconstruction over primary repair was based on early perception of the limited healing capacity of the ACL. Although the majority of ACL reconstruction surgeries successfully restore gross joint stability, post-traumatic osteoarthritis is commonplace following these injuries, even with ACL reconstruction. The development of new techniques to limit the long-term clinical sequelae associated with ACL reconstruction has been the main focus of research over the past decades. The improved knowledge of healing, along with recent advances in tissue engineering and regenerative medicine, has resulted in the discovery of novel biologically augmented ACL-repair techniques that have satisfactory outcomes in preclinical studies. This instructional review provides a summary of the latest advances made in ACL repair.

Cite this article: Bone Joint Res 2014;3:20–31.


Bone & Joint Research
Vol. 3, Issue 4 | Pages 89 - 94
1 Apr 2014
Cook JL Hung CT Kuroki K Stoker AM Cook CR Pfeiffer FM Sherman SL Stannard JP

Cartilage repair in terms of replacement, or regeneration of damaged or diseased articular cartilage with functional tissue, is the ‘holy grail’ of joint surgery. A wide spectrum of strategies for cartilage repair currently exists and several of these techniques have been reported to be associated with successful clinical outcomes for appropriately selected indications. However, based on respective advantages, disadvantages, and limitations, no single strategy, or even combination of strategies, provides surgeons with viable options for attaining successful long-term outcomes in the majority of patients. As such, development of novel techniques and optimisation of current techniques need to be, and are, the focus of a great deal of research from the basic science level to clinical trials. Translational research that bridges scientific discoveries to clinical application involves the use of animal models in order to assess safety and efficacy for regulatory approval for human use. This review article provides an overview of animal models for cartilage repair.

Cite this article: Bone Joint Res 2014;4:89–94.


Bone & Joint Research
Vol. 2, Issue 2 | Pages 18 - 25
1 Feb 2013
Kon E Filardo G Di Matteo B Perdisa F Marcacci M

Objectives

Matrix-assisted autologous chondrocyte transplantation (MACT) has been developed and applied in the clinical practice in the last decade to overcome most of the disadvantages of the first generation procedures. The purpose of this systematic review is to document and analyse the available literature on the results of MACT in the treatment of chondral and osteochondral lesions of the knee.

Methods

All studies published in English addressing MACT procedures were identified, including those that fulfilled the following criteria: 1) level I-IV evidence, 2) measures of functional or clinical outcome, 3) outcome related to cartilage lesions of the knee cartilage.


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.


Bone & Joint Research
Vol. 1, Issue 10 | Pages 238 - 244
1 Oct 2012
Naraoka T Ishibashi Y Tsuda E Yamamoto Y Kusumi T Kakizaki I Toh S

Objectives

This study aimed to investigate time-dependent gene expression of injured human anterior cruciate ligament (ACL), and to evaluate the histological changes of the ACL remnant in terms of cellular characterisation.

Methods

Injured human ACL tissues were harvested from 105 patients undergoing primary ACL reconstruction and divided into four phases based on the period from injury to surgery. Phase I was < three weeks, phase II was three to eight weeks, phase III was eight to 20 weeks, and phase IV was ≥ 21 weeks. Gene expressions of these tissues were analysed in each phase by quantitative real-time polymerase chain reaction using selected markers (collagen types 1 and 3, biglycan, decorin, α-smooth muscle actin, IL-6, TGF-β1, MMP-1, MMP-2 and TIMP-1). Immunohistochemical staining was also performed using primary antibodies against CD68, CD55, Stat3 and phosphorylated-Stat3 (P-Stat3).


Bone & Joint Research
Vol. 1, Issue 11 | Pages 281 - 288
1 Nov 2012
Conlisk N Gray H Pankaj P Howie CR

Objectives

Orthopaedic surgeons use stems in revision knee surgery to obtain stability when metaphyseal bone is missing. No consensus exists regarding stem size or method of fixation. This in vitro study investigated the influence of stem length and method of fixation on the pattern and level of relative motion at the bone–implant interface at a range of functional flexion angles.

Methods

A custom test rig using differential variable reluctance transducers (DVRTs) was developed to record all translational and rotational motions at the bone–implant interface. Composite femurs were used. These were secured to permit variation in flexion angle from 0° to 90°. Cyclic loads were applied through a tibial component based on three peaks corresponding to 0°, 10° and 20° flexion from a normal walking cycle. Three different femoral components were investigated in this study for cementless and cemented interface conditions.