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Bone & Joint Research
Vol. 14, Issue 2 | Pages 124 - 135
20 Feb 2025
Huang J Zheng J Yin J Lin R Wu J Xu H Zhu J Zhang H Wang G Cai D

Aims. To examine how eukaryotic translation initiation factor 5A (eIF5A) regulates osteoarthritis (OA) during mechanical overload and the specific mechanism. Methods. Histological experiments used human bone samples and C57BL/6J mice knee samples. All cell experiments were performed using mice primary chondrocytes. Messenger RNA (mRNA) sequencing was performed on chondrocytes treated with 20% cyclic tensile strain for 24 hours. Western blot (WB) and quantitative polymerase chain reaction were employed to detect relevant indicators of cartilage function in chondrocytes. We created the destabilization of the medial meniscus (DMM) model and the mechanical overload-induced OA model and injected with overexpressing eIF5A adenovirus (eIF5A-ADV). Cartilage degeneration was evaluated using Safranin O/Fast Green staining. Relative protein levels were ascertained by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Results. After OA initiation, eIF5A caused an upregulation of type II collagen (COL2) and a downregulation of matrix metalloproteinase 13 (MMP13), P16, and P21, which postponed the aggravation of OA. Further sequencing and experimental findings revealed that eIF5A knockdown accelerated the progression of OA by boosting the expression of histone acetyltransferase cyclic-adenosine monophosphate response element binding protein (CREB)-binding protein (CREBBP) to mediate activation of the Notch pathway. Conclusion. Our findings identified a crucial functional mechanism for the onset of OA, and suggest that intra-articular eIF5A injections might be a useful therapeutic strategy for OA treatment. Cite this article: Bone Joint Res 2025;14(2):124–135


Bone & Joint Research
Vol. 14, Issue 3 | Pages 199 - 207
5 Mar 2025
Largo R Mediero A Villa-Gomez C Bermejo-Alvarez I Herrero-Beaumont G

Osteoarthritis (OA) is a highly prevalent and disabling disease with an unmet therapeutic need. The characteristic cartilage loss and alteration of other joint structures result from a complex interaction of multiple risk factors, with mechanical overload consistently playing a central role. This overload generates an inflammatory response in the cartilage due to the activation of the innate immune response in chondrocytes, which occurs through various cellular mechanisms. Moreover, risk factors associated with obesity, being overweight, and metabolic syndrome enhance the inflammatory response both locally and systemically. OA chondrocytes, the only cells present in articular cartilage, are therefore inflamed and initiate an anabolic process in an attempt to repair the damaged tissue, which ultimately results in an aberrant and dysfunctional process. Under these circumstances, where the cartilage continues to be subjected to chronic mechanical stress, proposing a treatment that stimulates the chondrocytes’ anabolic response to restore tissue structure does not appear to be a therapeutic target with a high likelihood of success. In fact, anabolic drugs proposed for the treatment of OA have yet to demonstrate efficacy. By contrast, multiple therapeutic strategies focused on pharmacologically managing the inflammatory component, both at the joint and systemic levels, have shown promise. Therefore, prioritizing the control of chronic innate pro-inflammatory pathways presents the most viable and promising therapeutic strategy for the effective management of OA. As research continues, this approach may offer the best opportunity to alleviate the burden of this incapacitating disease. Cite this article: Bone Joint Res 2025;14(3):199–207


Bone & Joint Research
Vol. 14, Issue 3 | Pages 209 - 222
10 Mar 2025
Xiao Y Yue Z Zijing H Yao Z Sui M Xuemin Z Qiang Z Xiao Y Dapeng R

Aims. Excessive chondrocyte hypertrophy is a common feature in cartilage degeneration which is susceptible to joint overloading, but the relationship between mechanical overloading and chondrocyte hypertrophy still remains elusive. The aim of our study was to explore the mechanism of mechanical compression-induced chondrocyte hypertrophy. Methods. In this study, the temporomandibular joint (TMJ) degeneration model was built through forced mandibular retrusion (FMR)-induced compression in TMJ. Chondrocytes were also mechanically compressed in vitro. The role of O-GlcNAcylation in mechanical compression-induced chondrocyte hypertrophy manifested through specific activator Thiamet G and inhibitor OSMI-1. Results. Both in vivo and in vitro data revealed that chondrocyte hypertrophic differentiation is promoted by compression. Immunofluorescent and immunoblotting results showed that protein pan-O-GlcNAcylation levels were elevated in these hypertrophic chondrocytes. Pharmacologically inhibiting protein pan-O-GlcNAcylation by OSMI-1 partially mitigated the compression-induced hypertrophic differentiation of chondrocytes. Specifically, runt-related transcription factor 2 (Runx2) and SRY-Box 9 transcription factor (Sox9) were subjected to modification of O-GlcNAcylation under mechanical compression, and pharmacological activation or inhibition of O-GlcNAcylation affected the transcriptional activity of Runx2 but not Sox9. Furthermore, compression-induced protein pan-O-GlcNAcylation in chondrocytes was induced by enhanced expression of glucose transporter 1 (GLUT1), and depletion of GLUT1 by WZB117 dampened the effect of compression on chondrocyte hypertrophy. Conclusion. Our study proposes a novel function of GLUT1-mediated protein O-GlcNAcylation in driving compression-induced hypertrophic differentiation of chondrocytes by O-GlcNAc modification of Runx2, which promoted its transcriptional activity and strengthened the expressions of downstream hypertrophic marker. Cite this article: Bone Joint Res 2025;14(3):209–222


Bone & Joint Research
Vol. 1, Issue 10 | Pages 245 - 257
1 Oct 2012
Tibor LM Leunig M

Femoroacetabular impingement (FAI) causes pain and chondrolabral damage via mechanical overload during movement of the hip. It is caused by many different types of pathoanatomy, including the cam ‘bump’, decreased head–neck offset, acetabular retroversion, global acetabular overcoverage, prominent anterior–inferior iliac spine, slipped capital femoral epiphysis, and the sequelae of childhood Perthes’ disease. Both evolutionary and developmental factors may cause FAI. Prevalence studies show that anatomic variations that cause FAI are common in the asymptomatic population. Young athletes may be predisposed to FAI because of the stress on the physis during development. Other factors, including the soft tissues, may also influence symptoms and chondrolabral damage. FAI and the resultant chondrolabral pathology are often treated arthroscopically. Although the results are favourable, morphologies can be complex, patient expectations are high and the surgery is challenging. The long-term outcomes of hip arthroscopy are still forthcoming and it is unknown if treatment of FAI will prevent arthrosis


The Journal of Bone & Joint Surgery British Volume
Vol. 45-B, Issue 4 | Pages 755 - 760
1 Nov 1963
Ondrouch AS

1. The cause of cyst formation lies in the major overloading of certain regions caused by the unevenness of the articular surface produced by the arthritic process. 2. Photoelasticity investigations disclose an overburdening of the bone beneath the surface of the joint, which in turn markedly resembles the shapes of actual cysts. 3. The results of this investigation fit organically into the logical sequence of processes in accordance with our theory. 4. This theory is further borne out by the successful formation of cyst phenomena in healthy joints by overloading (Trias 1961). 5. Our theory has no immediate practical bearing on the treatment of arthritic cysts. However, it uncovers certain interesting aspects of the behaviour of bone tissues under mechanical overloading above the limits of biological, though below those of mechanical bearing capacity. Conclusions arising therefrom might in many respects be useful in research into the physiology of bone


Bone & Joint 360
Vol. 13, Issue 5 | Pages 24 - 26
1 Oct 2024

The October 2024 Knee Roundup360 looks at: Managing the unexpected: treatment of intraoperative medial collateral ligament injuries; Identifying subgroups of patients that may benefit from robotic arm-assisted total knee arthroplasty: secondary analysis of data from a randomized controlled trial; Cost-effectiveness of enoxaparin versus aspirin in the prevention of venous thromboembolism after total hip or knee arthroplasty: an analysis from the CRISTAL cluster-randomized trial; Cartilage regeneration and long-term survival in medial knee osteoarthritis patients treated with high tibial osteotomy and osteochondral autologous transfer system; Treatment of chronic and complex meniscal tears with arthroscopic meniscus repair augmented with collagen matrix wrapping: failure rate and functional outcomes; Long-term outcomes of multiligament knee injuries in American football players.


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1416 - 1425
1 Dec 2024
Stroobant L Jacobs E Arnout N Van Onsem S Tampere T Burssens A Witvrouw E Victor J

Aims

Approximately 10% to 20% of knee arthroplasty patients are not satisfied with the result, while a clear indication for revision surgery might not be present. Therapeutic options for these patients, who often lack adequate quadriceps strength, are limited. Therefore, the primary aim of this study was to evaluate the clinical effect of a novel rehabilitation protocol that combines low-load resistance training (LL-RT) with blood flow restriction (BFR).

Methods

Between May 2022 and March 2024, we enrolled 45 dissatisfied knee arthroplasty patients who lacked any clear indication for revision to this prospective cohort study. All patients were at least six months post-surgery and had undergone conventional physiotherapy previously. The patients participated in a supervised LL-RT combined with BFR in 18 sessions. Primary assessments included the following patient-reported outcome measures (PROMs): Knee injury and Osteoarthritis Outcome Score (KOOS); Knee Society Score: satisfaction (KSSs); the EuroQol five-dimension five-level questionnaire (EQ-5D-5L); and the pain catastrophizing scale (PCS). Functionality was assessed using the six-minute walk Test (6MWT) and the 30-second chair stand test (30CST). Follow-up timepoints were at baseline, six weeks, three months, and six months after the start.


The Bone & Joint Journal
Vol. 107-B, Issue 2 | Pages 268 - 276
1 Feb 2025
Hedley PL Lausten-Thomsen U Conway KM Hindsø K Romitti PA Christiansen M

Aims

In this study, we aimed to evaluate incidence trends and potential risk factors associated with Perthes’ disease in Denmark, using publicly available data.

Methods

Our population-based case-control study used data from the Danish National Patient Register and Danish Civil Registration System, accessed through the publicly available Danish Biobank Register, to identify 1,924,292 infants born between 1985 and 2016. We estimated age-specific incidence rates for four birth periods of equal duration (1985 to 1992, 1993 to 2000, 2001 to 2008, and 2009 to 2016) and investigated associations with perinatal conditions, congenital malformations, coagulation defects, autism spectrum disorders (ASD), and attention deficit hyperactivity disorders (ADHD).


Bone & Joint Open
Vol. 2, Issue 6 | Pages 443 - 456
28 Jun 2021
Thompson JW Corbett J Bye D Jones A Tissingh EK Nolan J

Aims

The Exeter V40 cemented polished tapered stem system has demonstrated excellent long-term outcomes. This paper presents a systematic review of the existing literature and reports on a large case series comparing implant fractures between the Exeter V40 series; 125 mm and conventional length stem systems.

Methods

A systematic literature search was performed adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. In parallel, we performed a retrospective single centre study of Exeter V40 femoral stem prosthetic fractures between April 2003 and June 2020.


The Bone & Joint Journal
Vol. 103-B, Issue 9 | Pages 1472 - 1478
1 Sep 2021
Shoji T Saka H Inoue T Kato Y Fujiwara Y Yamasaki T Yasunaga Y Adachi N

Aims

Rotational acetabular osteotomy (RAO) has been reported to be effective in improving symptoms and preventing osteoarthritis (OA) progression in patients with mild to severe develomental dysplasia of the hip (DDH). However, some patients develop secondary OA even when the preoperative joint space is normal; determining who will progress to OA is difficult. We evaluated whether the preoperative cartilage condition may predict OA progression following surgery using T2 mapping MRI.

Methods

We reviewed 61 hips with early-stage OA in 61 patients who underwent RAO for DDH. They underwent preoperative and five-year postoperative radiological analysis of the hip. Those with a joint space narrowing of more than 1 mm were considered to have 'OA progression'. Preoperative assessment of articular cartilage was also performed using 3T MRI with the T2 mapping technique. The region of interest was defined as the weightbearing portion of the acetabulum and femoral head.


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.


The Bone & Joint Journal
Vol. 102-B, Issue 1 | Pages 55 - 63
1 Jan 2020
Hagberg K Ghassemi Jahani S Kulbacka-Ortiz K Thomsen P Malchau H Reinholdt C

Aims

The aim of this study was to describe implant and patient-reported outcome in patients with a unilateral transfemoral amputation (TFA) treated with a bone-anchored, transcutaneous prosthesis.

Methods

In this cohort study, all patients with a unilateral TFA treated with the Osseointegrated Prostheses for the Rehabilitation of Amputees (OPRA) implant system in Sahlgrenska University Hospital, Gothenburg, Sweden, between January 1999 and December 2017 were included. The cohort comprised 111 patients (78 male (70%)), with a mean age 45 years (17 to 70). The main reason for amputation was trauma in 75 (68%) and tumours in 23 (21%). Patients answered the Questionnaire for Persons with Transfemoral Amputation (Q-TFA) before treatment and at two, five, seven, ten, and 15 years’ follow-up. A prosthetic activity grade was assigned to each patient at each timepoint. All mechanical complications, defined as fracture, bending, or wear to any part of the implant system resulting in removal or change, were recorded.


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.


Bone & Joint 360
Vol. 6, Issue 6 | Pages 14 - 16
1 Dec 2017


The Bone & Joint Journal
Vol. 97-B, Issue 7 | Pages 982 - 987
1 Jul 2015
Ganesan S Karampalis C Garrido E Tsirikos AI

Acute angulation at the thoracolumbar junction with segmental subluxation of the spine occurring at the level above an anteriorly hypoplastic vertebra in otherwise normal children is a rare condition described as infantile developmental thoracolumbar kyphosis. Three patient series with total of 18 children have been reported in the literature. We report five children who presented with thoracolumbar kyphosis and discuss the treatment algorithm. We reviewed the medical records and spinal imaging at initial clinical presentation and at minimum two-year follow-up. The mean age at presentation was eight months (two to 12). All five children had L2 anterior vertebral body hypoplasia. The kyphosis improved spontaneously in three children kept under monitoring. In contrast, the deformity was progressive in two patients who were treated with bracing. The kyphosis and segmental subluxation corrected at latest follow-up (mean age 52 months; 48 to 60) in all patients with near complete reconstitution of the anomalous vertebra. The deformity and radiological imaging on a young child can cause anxiety to both parents and treating physicians. Diagnostic workup and treatment algorithm in the management of infantile developmental thoracolumbar kyphosis is proposed. Observation is indicated for non-progressive kyphosis and bracing if there is evidence of kyphosis and segmental subluxation deterioration beyond walking age. Surgical stabilisation of the spine can be reserved for severe progressive deformities unresponsive to conservative treatment.

Cite this article: Bone Joint J 2015;97-B:982–7.


The Bone & Joint Journal
Vol. 96-B, Issue 1 | Pages 106 - 113
1 Jan 2014
Brånemark R Berlin Ö Hagberg K Bergh P Gunterberg B Rydevik B

Patients with transfemoral amputation (TFA) often experience problems related to the use of socket-suspended prostheses. The clinical development of osseointegrated percutaneous prostheses for patients with a TFA started in 1990, based on the long-term successful results of osseointegrated dental implants.

Between1999 and 2007, 51 patients with 55 TFAs were consecutively enrolled in a prospective, single-centre non-randomised study and followed for two years. The indication for amputation was trauma in 33 patients (65%) and tumour in 12 (24%). A two-stage surgical procedure was used to introduce a percutaneous implant to which an external amputation prosthesis was attached. The assessment of outcome included the use of two self-report questionnaires, the Questionnaire for Persons with a Transfemoral Amputation (Q-TFA) and the Short-Form (SF)-36.

The cumulative survival at two years’ follow-up was 92%. The Q-TFA showed improved prosthetic use, mobility, global situation and fewer problems (all p < 0.001). The physical function SF-36 scores were also improved (p < 0.001). Superficial infection was the most frequent complication, occurring 41 times in 28 patients (rate of infection 54.9%). Most were treated effectively with oral antibiotics. The implant was removed in four patients because of loosening (three aseptic, one infection).

Osseointegrated percutaneous implants constitute a novel form of treatment for patients with TFA. The high cumulative survival rate at two years (92%) combined with enhanced prosthetic use and mobility, fewer problems and improved quality of life, supports the ‘revolutionary change’ that patients with TFA have reported following treatment with osseointegrated percutaneous prostheses.

Cite this article: Bone Joint J 2014;96-B:106–13.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 2 | Pages 243 - 244
1 Feb 2008
Tsaridis E Sarikloglou S Papasoulis E Lykoudis S Koutroumpas I Avtzakis V

A 64-year-old man presented with a severe deformity of the tibia caused by Paget’s disease and osteoarthritis of the ipsilateral knee. Total knee replacement required preliminary correction of the tibial deformity. This was successfully achieved by tibial osteotomy followed by distraction osteogenesis using the Taylor spatial frame. The subsequent knee replacement was successful, with no recurrence of deformity.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 3 | Pages 430 - 435
1 Mar 2010
Tsirikos AI McMaster MJ

We report five children who presented at the mean age of 1.5 years (1.1 to 1.9) with a progressive thoracolumbar kyphosis associated with segmental instability and subluxation of the spine at the level above an anteriorly-wedged hypoplastic vertebra at L1 or L2. The spinal deformity appeared to be developmental and not congenital in origin. The anterior wedging of the vertebra may have been secondary to localised segmental instability and subsequent kyphotic deformity.

We suggest the term ‘infantile developmental thoracolumbar kyphosis with segmental subluxation of the spine’ to differentiate this type of deformity from congenital displacement of the spine in which the congenital vertebral anomaly does not resolve. Infantile developmental kyphosis with segmental subluxation of the spine, if progressive, may carry the risk of neurological compromise. In all of our patients the kyphotic deformity progressed over a period of three months and all were treated by localised posterior spinal fusion. At a mean follow-up of 6.6 years (5.0 to 9.0), gradual correction of the kyphosis was seen on serial radiographs as well as reconstitution of the hypoplastic wedged vertebra to normality. Exploration of the arthrodesis was necessary at nine months in one patient who developed a pseudarthrosis.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 3 | Pages 448 - 453
1 Mar 2010
Benson RT McDonnell SM Knowles HJ Rees JL Carr AJ Hulley PA

The aim of this study was to investigate the occurrence of tissue hypoxia and apoptosis at different stages of tendinopathy and tears of the rotator cuff.

We studied tissue from 24 patients with eight graded stages of either impingement (mild, moderate and severe) or tears of the rotator cuff (partial, small, medium, large and massive) and three controls. Biopsies were analysed using three immunohistochemical techniques, namely antibodies against HIF-1α (a transcription factor produced in a hypoxic environment), BNip3 (a HIF-1α regulated pro-apoptotic protein) and TUNEL (detecting DNA fragmentation in apoptosis).

The HIF-1α expression was greatest in mild impingement and in partial, small, medium and large tears. BNip3 expression increased significantly in partial, small, medium and large tears but was reduced in massive tears. Apoptosis was increased in small, medium, large and massive tears but not in partial tears.

These findings reveal evidence of hypoxic damage throughout the spectrum of pathology of the rotator cuff which may contribute to loss of cells by apoptosis. This provides a novel insight into the causes of degeneration of the rotator cuff and highlights possible options for treatment.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 4 | Pages 445 - 449
1 Apr 2005
Smith GD Knutsen G Richardson JB