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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 Research
Vol. 12, Issue 10 | Pages 624 - 635
4 Oct 2023
Harrison CJ Plessen CY Liegl G Rodrigues JN Sabah SA Beard DJ Fischer F

Aims

To map the Oxford Knee Score (OKS) and High Activity Arthroplasty Score (HAAS) items to a common scale, and to investigate the psychometric properties of this new scale for the measurement of knee health.

Methods

Patient-reported outcome measure (PROM) data measuring knee health were obtained from the NHS PROMs dataset and Total or Partial Knee Arthroplasty Trial (TOPKAT). Assumptions for common scale modelling were tested. A graded response model (fitted to OKS item responses in the NHS PROMs dataset) was used as an anchor to calibrate paired HAAS items from the TOPKAT dataset. Information curves for the combined OKS-HAAS model were plotted. Bland-Altman analysis was used to compare common scale scores derived from OKS and HAAS items. A conversion table was developed to map between HAAS, OKS, and the common scale.


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 Research
Vol. 11, Issue 9 | Pages 619 - 628
7 Sep 2022
Yapp LZ Scott CEH Howie CR MacDonald DJ Simpson AHRW Clement ND

Aims

The aim of this study was to report the meaningful values of the EuroQol five-dimension three-level questionnaire (EQ-5D-3L) and EuroQol visual analogue scale (EQ-VAS) in patients undergoing primary knee arthroplasty (KA).

Methods

This is a retrospective study of patients undergoing primary KA for osteoarthritis in a university teaching hospital (Royal Infirmary of Edinburgh) (1 January 2013 to 31 December 2019). Pre- and postoperative (one-year) data were prospectively collected for 3,181 patients (median age 69.9 years (interquartile range (IQR) 64.2 to 76.1); females, n = 1,745 (54.9%); median BMI 30.1 kg/m2 (IQR 26.6 to 34.2)). The reliability of the EQ-5D-3L was measured using Cronbach’s alpha. Responsiveness was determined by calculating the anchor-based minimal clinically important difference (MCID), the minimal important change (MIC) (cohort and individual), the patient-acceptable symptom state (PASS) predictive of satisfaction, and the minimal detectable change at 90% confidence intervals (MDC-90).


Bone & Joint Research
Vol. 11, Issue 7 | Pages 494 - 502
20 Jul 2022
Kwon HM Lee J Koh Y Park KK Kang K

Aims

A functional anterior cruciate ligament (ACL) or posterior cruciate ligament (PCL) has been assumed to be required for patients undergoing unicompartmental knee arthroplasty (UKA). However, this assumption has not been thoroughly tested. Therefore, this study aimed to assess the biomechanical effects exerted by cruciate ligament-deficient knees with medial UKAs regarding different posterior tibial slopes.

Methods

ACL- or PCL-deficient models with posterior tibial slopes of 1°, 3°, 5°, 7°, and 9° were developed and compared to intact models. The kinematics and contact stresses on the tibiofemoral joint were evaluated under gait cycle loading conditions.


Bone & Joint Research
Vol. 10, Issue 4 | Pages 269 - 276
1 Apr 2021
Matsubara N Nakasa T Ishikawa M Tamura T Adachi N

Aims

Meniscal injuries are common and often induce knee pain requiring surgical intervention. To develop effective strategies for meniscus regeneration, we hypothesized that a minced meniscus embedded in an atelocollagen gel, a firm gel-like material, may enhance meniscus regeneration through cell migration and proliferation in the gel. Hence, the objective of this study was to investigate cell migration and proliferation in atelocollagen gels seeded with autologous meniscus fragments in vitro and examine the therapeutic potential of this combination in an in vivo rabbit model of massive meniscus defect.

Methods

A total of 34 Japanese white rabbits (divided into defect and atelocollagen groups) were used to produce the massive meniscus defect model through a medial patellar approach. Cell migration and proliferation were evaluated using immunohistochemistry. Furthermore, histological evaluation of the sections was performed, and a modified Pauli’s scoring system was used for the quantitative evaluation of the regenerated meniscus.


Aims

Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells’ activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells.

Methods

Cell viability, proliferation, migration, and expression levels of Collagen-I (COL-I) A1, transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) were compared between ACL remnant cells untreated and treated with ESW (0.15 mJ/mm2, 1,000 impulses, 4 Hz). To evaluate the subsequent effects on the surrounding cells, bone marrow stromal cells (BMSCs)’ viability, proliferation, migration, and levels of Type I Collagen, Type III Collagen, and tenogenic gene (Scx, TNC) expression were investigated using coculture system.


Bone & Joint Research
Vol. 9, Issue 9 | Pages 593 - 600
1 Sep 2020
Lee J Koh Y Kim PS Kang KW Kwak YH Kang K

Aims

Unicompartmental knee arthroplasty (UKA) has become a popular method of treating knee localized osteoarthritis (OA). Additionally, the posterior cruciate ligament (PCL) is essential to maintaining the physiological kinematics and functions of the knee joint. Considering these factors, the purpose of this study was to investigate the biomechanical effects on PCL-deficient knees in medial UKA.

Methods

Computational simulations of five subject-specific models were performed for intact and PCL-deficient UKA with tibial slopes. Anteroposterior (AP) kinematics and contact stresses of the patellofemoral (PF) joint and the articular cartilage were evaluated under the deep-knee-bend condition.


Bone & Joint Research
Vol. 8, Issue 12 | Pages 593 - 600
1 Dec 2019
Koh Y Lee J Lee H Kim H Chung H Kang K

Aims

Commonly performed unicompartmental knee arthroplasty (UKA) is not designed for the lateral compartment. Additionally, the anatomical medial and lateral tibial plateaus have asymmetrical geometries, with a slightly dished medial plateau and a convex lateral plateau. Therefore, this study aims to investigate the native knee kinematics with respect to the tibial insert design corresponding to the lateral femoral component.

Methods

Subject-specific finite element models were developed with tibiofemoral (TF) and patellofemoral joints for one female and four male subjects. Three different TF conformity designs were applied. Flat, convex, and conforming tibial insert designs were applied to the identical femoral component. A deep knee bend was considered as the loading condition, and the kinematic preservation in the native knee was investigated.


Bone & Joint Research
Vol. 8, Issue 10 | Pages 495 - 501
1 Oct 2019
Hampp EL Sodhi N Scholl L Deren ME Yenna Z Westrich G Mont MA

Objectives

The use of the haptically bounded saw blades in robotic-assisted total knee arthroplasty (RTKA) can potentially help to limit surrounding soft-tissue injuries. However, there are limited data characterizing these injuries for cruciate-retaining (CR) TKA with the use of this technique. The objective of this cadaver study was to compare the extent of soft-tissue damage sustained through a robotic-assisted, haptically guided TKA (RATKA) versus a manual TKA (MTKA) approach.

Methods

A total of 12 fresh-frozen pelvis-to-toe cadaver specimens were included. Four surgeons each prepared three RATKA and three MTKA specimens for cruciate-retaining TKAs. A RATKA was performed on one knee and a MTKA on the other. Postoperatively, two additional surgeons assessed and graded damage to 14 key anatomical structures in a blinded manner. Kruskal–Wallis hypothesis tests were performed to assess statistical differences in soft-tissue damage between RATKA and MTKA cases.


Bone & Joint Research
Vol. 7, Issue 1 | Pages 20 - 27
1 Jan 2018
Kang K Son J Suh D Kwon SK Kwon O Koh Y

Objectives

Patient-specific (PS) implantation surgical technology has been introduced in recent years and a gradual increase in the associated number of surgical cases has been observed. PS technology uses a patient’s own geometry in designing a medical device to provide minimal bone resection with improvement in the prosthetic bone coverage. However, whether PS unicompartmental knee arthroplasty (UKA) provides a better biomechanical effect than standard off-the-shelf prostheses for UKA has not yet been determined, and still remains controversial in both biomechanical and clinical fields. Therefore, the aim of this study was to compare the biomechanical effect between PS and standard off-the-shelf prostheses for UKA.

Methods

The contact stresses on the polyethylene (PE) insert, articular cartilage and lateral meniscus were evaluated in PS and standard off-the-shelf prostheses for UKA using a validated finite element model. Gait cycle loading was applied to evaluate the biomechanical effect in the PS and standard UKAs.


Objectives

Posterior condylar offset (PCO) and posterior tibial slope (PTS) are critical factors in total knee arthroplasty (TKA). A computational simulation was performed to evaluate the biomechanical effect of PCO and PTS on cruciate retaining TKA.

Methods

We generated a subject-specific computational model followed by the development of ± 1 mm, ± 2 mm and ± 3 mm PCO models in the posterior direction, and -3°, 0°, 3° and 6° PTS models with each of the PCO models. Using a validated finite element (FE) model, we investigated the influence of the changes in PCO and PTS on the contact stress in the patellar button and the forces on the posterior cruciate ligament (PCL), patellar tendon and quadriceps muscles under the deep knee-bend loading conditions.


Bone & Joint Research
Vol. 6, Issue 11 | Pages 623 - 630
1 Nov 2017
Suh D Kang K Son J Kwon O Baek C Koh Y

Objectives

Malalignment of the tibial component could influence the long-term survival of a total knee arthroplasty (TKA). The object of this study was to investigate the biomechanical effect of varus and valgus malalignment on the tibial component under stance-phase gait cycle loading conditions.

Methods

Validated finite element models for varus and valgus malalignment by 3° and 5° were developed to evaluate the effect of malalignment on the tibial component in TKA. Maximum contact stress and contact area on a polyethylene insert, maximum contact stress on patellar button and the collateral ligament force were investigated.


Objectives

The lack of effective treatment for cartilage defects has prompted investigations using tissue engineering techniques for their regeneration and repair. The success of tissue-engineered repair of cartilage may depend on the rapid and efficient adhesion of transplanted cells to a scaffold. Our aim in this study was to repair full-thickness defects in articular cartilage in the weight-bearing area of a porcine model, and to investigate whether the CD44 monoclonal antibody biotin-avidin (CBA) binding technique could provide satisfactory tissue-engineered cartilage.

Methods

Cartilage defects were created in the load-bearing region of the lateral femoral condyle of mini-type pigs. The defects were repaired with traditional tissue-engineered cartilage, tissue-engineered cartilage constructed with the biotin-avidin (BA) technique, tissue-engineered cartilage constructed with the CBA technique and with autologous cartilage. The biomechanical properties, Western blot assay, histological findings and immunohistochemical staining were explored.


Bone & Joint Research
Vol. 5, Issue 3 | Pages 80 - 86
1 Mar 2016
Scott G Imam MA Eifert A Freeman MAR Pinskerova V Field RE Skinner J Banks SA

Objectives

Throughout the 20th Century, it has been postulated that the knee moves on the basis of a four-bar link mechanism composed of the cruciate ligaments, the femur and the tibia. As a consequence, the femur has been thought to roll back with flexion, and total knee arthroplasty (TKA) prostheses have been designed on this basis. Recent work, however, has proposed that at a position of between 0° and 120° the medial femoral condyle does not move anteroposteriorly whereas the lateral femoral condyle tends, but is not obliged, to roll back – a combination of movements which equates to tibial internal/ femoral external rotation with flexion. The aim of this paper was to assess if the articular geometry of the GMK Sphere TKA could recreate the natural knee movements in situ/in vivo.

Methods

The pattern of knee movement was studied in 15 patients (six male: nine female; one male with bilateral TKAs) with 16 GMK Sphere implants, at a mean age of 66 years (53 to 76) with a mean BMI of 30 kg/m2 (20 to 35). The motions of all 16 knees were observed using pulsed fluoroscopy during a number of weight-bearing and non-weight-bearing static and dynamic activities.


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 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.


Bone & Joint Research
Vol. 3, Issue 4 | Pages 108 - 116
1 Apr 2014
Cheng K Giebaly D Campbell A Rumley A Lowe G

Objective

Mortality rates reported by the National Joint Registry for England and Wales (NJR) were higher following cemented total knee replacement (TKR) compared with uncemented procedures. The aim of this study is to examine and compare the effects of cemented and uncemented TKR on the activation of selected markers of inflammation, endothelium, and coagulation, and on the activation of selected cytokines involved in the various aspects of the systemic response following surgery.

Methods

This was a single centre, prospective, case-control study. Following enrolment, blood samples were taken pre-operatively, and further samples were collected at day one and day seven post-operatively. One patient in the cemented group developed a deep-vein thrombosis confirmed on ultrasonography and was excluded, leaving 19 patients in this cohort (mean age 67.4, (sd 10.62)), and one patient in the uncemented group developed a post-operative wound infection and was excluded, leaving 19 patients (mean age 66.5, (sd 7.82)).