Approximately 15–20% of patients report chronic pain three months after total knee replacement (TKR). The STAR care pathway is a clinically important and cost-effective personalised intervention for patients with pain 3 months after TKR. The pathway comprises screening, assesment, onward referral for treatment and follow-up over one year. In a multicentre randomised controlled trial comparing the pathway with usual care, the pathway improved pain at 6 and 12 months. This study examined the longer-term clinical and cost-effectiveness of the STAR care pathway. STAR trial participants were followed-up at a median of 4 years post-randomisation. Co-primary outcomes were self-reported pain severity and interference in the replaced knee, assessed with the Brief Pain Inventory (BPI). Resource use from electronic hospital records was valued with UK reference costs.Abstract
Introduction
Methodology
The purpose was to determine the lifetime risk of re-operation due to specific complications related to dual mobility using re-operation as a competing risk, excluding loosening, periprosthetic fracture, and infection. 1503 mono-block dual mobility total hip arthroplasty (DM-THAs). Defining the re-operation when anesthesia (for dislocation) and revision when the implant changed. Surgery (801 for primary, 702 for revision with 201 for recurrent dislocation and 501 for loosening) performed between 1990 and 2020 in average 81-year-old (range 50–102) patients, with 522 living patients at 10 years follow-up.
The 522 patients followed ten years or more had a 15% risk revision due to DM specific complications during their lifetime and 10% more risk associated with loosening (6%), periprosthetic fracture (2%) and infection (2%).
Complex regional pain syndrome type 1 (CRPS-I) is a devastating complication that can occur after limb extremity injuries. The effectiveness of vitamin C in preventing CRPS-I incidence is debatable. Therefore, we conducted a systematic review and meta-analysis to assess the role of vitamin C in CRPS-I prevention and its effect on pain score, functional outcomes and complications rate after wrist, ankle, and foot fractures. We searched Medline, Embase, the Cochrane Library, Clinicaltrial.gov, and Google Scholar from infinity to May 2021 for relevant studies comparing the incidence of CRPS-I with administration of perioperative vitamin C versus placebo after wrist, ankle, and foot fractures. Continuous data such as functional outcomes and pain scores were pooled as mean differences (MD), whist dichotomous variables such as the incidence of CRPS-I and complications were pooled as odds ratios (OR), with 95% confidence interval (CI). Data analyses was done using R software (meta package, version 4.9-0) for Windows. Eight studies, including two quasi-experimental studies, were included. The timeframe for vitamin C administration ranged from 42 to 50 days post-injury and/or surgical fixation and the dosage was either 500 mg or 1000 mg. The results showed that vitamin C was associated with a lower rate of CRPS-I relative to a placebo (OR 0.33, 95% CI [0.17, 0.63]). No significant difference was found between vitamin C and placebo in terms of complications (OR 1.90, 95% CI [0.99, 3.65]), functional outcomes (MD 6.37, 95% CI [-1.40, 14.15]), and pain scores (MD −0.14, 95% CI [-1.07, 0.79]). The findings demonstrate that when compared to placebo, at least 42 days of vitamin C prophylaxis is associated with prevention of CRPS-I following wrist, ankle, and foot fractures, irrespective of vitamin C dosage or fracture type. No significant differences were found with secondary outcomes.
Ankle fractures represent the third most common fragility fracture seen in elderly patients following hip and distal radius fractures. Non-operative management of these see complication rates as high as 70%. Open reduction and internal fixation (ORIF) has complication rates of up to 40%. With either option, patients tend to be managed with a non-weight bearing period of six weeks or longer. An alternative is the use of a tibiotalocalcaneal (TTC) nail. This provides a percutaneous treatment that enables the patient to mobilise immediately. This case-series explores the efficacy of this device in a broad population, including the highly comorbid and cognitively impaired. We reviewed patients treated with TTC nail for acute ankle fractures between 2019 and 2022. Baseline and surgical data were collected. Clinical records were reviewed to record any post-operative complication, and post-operative mobility status and domicile. 24 patients had their ankle fracture managed with TTC nailing. No intra-operative complications were noted. There were six (27%) post-operative complications; four patients had loosening of a distal locking screw, one significant wound infection necessitating exchange of nail, and one pressure area from an underlying displaced fracture fragment. All except three patients returned to their previous domicile. Just over two thirds of patients returned to their baseline level of mobility. This case-series is one of the largest and is also one of the first to include cognitively impaired patients. Our results are consistent with other case-series with a favourable complication rate when compared with ORIF in similar patient groups. The use of a TTC nail in the context of acute, geriatric ankle trauma is a simple and effective treatment modality. This series shows acceptable complication rates and the majority of patients are able to return to their baseline level of mobility and domicile.
Distal radius fractures are common in South Africa. Accurate, decisive radiographic parameter interpretation is key in appropriate management. Digital radiographic facilities are rare in the public setting and goniometer usage is known to be low, thus, visual estimates are the primary form of radiographic assessment. Previous research associated orthopaedic experience with accuracy of distal radius fracture parameter estimation but, oftentimes, doctors treating orthopaedic patients are not experienced in orthopaedics. A cross-sectional questionnaire including four distal radius fracture radiographs administered to 149 orthopaedic doctors at three Johannesburg teaching hospitals. Participants grouped into ranks of: consultants (n=36), registrars (n=41), medical officers (n=20) and interns (n=52). Participants visually estimated values of distal radius fracture parameters, stated whether they would accept the position of the fractures and stated their percentage of routine usage of goniometers in real practice. The registrar group was most accurate in visually estimating radial height, whilst the interns were least accurate (p=0.0237). The consultant, registrar and medical officer groups were equally accurate in estimating radial inclination whilst the intern group was the least accurate (p<0.0001). The consultant and registrar group were equally accurate at estimating volar tilt, whilst the medical officer and intern groups were least accurate (p<0.0001). The Gwet's AC agreement was 0.1612 (p=0.047) for acceptance of position of the first radiograph, 0.8768 (p<0.0001) for the second, 0.8884 (p<0.0001) for the third and 0.8064 (p<0.0001) for the fourth. All groups showed no difference in goniometer usage, using them largely 0–25% of practice (p=0.1937). The study found that accuracy in visual estimations of distal radius fracture parameters was linked to orthopaedic experience but not linked to routine practice goniometer usage, which was minimal across all groups. Inter-rater agreement on acceptability of fracture position is potentially dependent on severity of deviation from acceptable parameters.
There is a paucity of mid-term data on modular dual-mobility (MDM) constructs versus large (≥40 mm) femoral heads (LFH) in revision total hip arthroplasties (THAs). The purpose of this study was to update our prior series at 10 years, with specific emphasis on survivorships free of re-revision for dislocation, any re-revision, and dislocation. We identified 300 revision THAs performed at a single tertiary care academic institution from 2011 to 2014. Aseptic loosening of the acetabular component (n=65), dislocation (n=59), and reimplantation as part of a two-stage exchange protocol (n=57) were the most common reasons for index revision. Dual-mobility constructs were used in 124 cases, and LFH were used in 176 cases. Mean age was 66 years, mean BMI was 31 kg/m2, and 45% were female. Mean follow-up was 7 years. The 10-year survivorship free of re-revision for dislocation was 97% in the MDM cohort and 91% in the LFH cohort with a significantly increased risk of re-revision for dislocation in the LFH cohort (HR 5.2; p=0.03). The 10-year survivorship free of any re-revision was 90% in the MDM cohort and 84% in the LFH cohort with a significantly increased risk of any re-revision in the LFH cohort (HR 2.5; p=0.04). The 10-year survivorship free of any dislocation was 92% in the MDM cohort and 87% in the LFH cohort. There was a trend towards an increased risk of any dislocation in the LFH cohort (HR 2.3; p=0.06). In this head-to-head comparison, revision THAs using MDM constructs had a significantly lower risk of re-revision for dislocation compared to LFH at 10 years. In addition, there was a trend towards lower risk of any dislocation. Level of Evidence: IV
Fractures of the distal radius are common, and form a considerable proportion of the trauma workload. We conducted a study to examine the patterns of injury and treatment for adult patients presenting with distal radius fractures to a major trauma centre serving an urban population. We undertook a retrospective cohort study to identify all patients treated at our major trauma centre for a distal radius fracture between 1 June 2018 and 1 May 2021. We reviewed the medical records and imaging for each patient to examine patterns of injury and treatment. We undertook a binomial logistic regression to produce a predictive model for operative fixation or inpatient admission. Overall, 571 fractures of the distal radius were treated at our centre during the study period. A total of 146 (26%) patients required an inpatient admission, and 385 surgical procedures for fractures of the distal radius were recorded between June 2018 and May 2021. The most common mechanism of injury was a fall from a height of one metre or less. Of the total fractures, 59% (n = 337) were treated nonoperatively, and of those patients treated with surgery, locked anterior-plate fixation was the preferred technique (79%; n = 180). The epidemiology of distal radius fractures treated at our major trauma centre replicated the classical bimodal distribution described in the literature. Patient age, open fractures, and fracture classification were factors correlated with the decision to treat the fracture operatively. While most fractures were
Hemi-arthroplasty (HA) as a treatment for fractured neck of femur has slightly increased since 2019 and remarkably after the COVID pandemic. The main drawback of the treatment is ongoing cartilage deterioration that may require revision to THR. This study assessed cartilage surface damage in hip HA by reproducing anatomical motion and loading conditions in a hip simulator.Abstract
BACKGROUND
OBJECTIVE
Atypical femoral fracture non-union (AFFNU) is both, rare (3–5 per 1000 proximal femur fractures) and difficult to treat. Lack of standardised guidelines leads to a variability in fixation constructs, use of bone grafting and restricted weight bearing protocols, which are not evidence based. We hypothesised that there is no change in union rates without the use of bone grafting and immediate weight bearing post-operatively does not lead to increased complications. A retrospective review of all consecutively treated AFFNU cases between March 2015 to December 2019 was carried out. 9 patients with a mean age of 63.87 years and M:F ratio of 7:2 met the inclusion criteria. Primary outcome variable was radiographic union at 12 months after revision surgery. All surgeries were carried out by a single surgeon. Fixation construct, neck-shaft angle, use of bone graft and immediate postoperative weight bearing protocols were recorded. Radiographic union was achieved in 7 of 9 patients (78%) after first revision surgery. 1 patient achieved union after 2nd revision surgery and 1 patient died in the early post-operative period due to pulmonary embolism. No bone grafting was used in any of the patients and weight-bearing as tolerated was allowed from the first post-operative day. The mean neck-shaft angle after non-union surgery was 136 degrees.Materials & Methods
Results
The purpose of this study is to assess the long term results of combined ACL reconstruction and unicompartmental knee replacements (UKR). These patients have been selected for this combined operation due to their combination of instability symptoms from an absent ACL and unicompartmental arthritis. Retrospective review of 44 combined UKR and ACL reconstruction by a single surgeon. Surgeries included both medial and lateral UKR combined with either revision ACL reconstruction or primary ACL reconstruction. Patient reported outcomes were obtained preoperatively, at one year, 5 years and 10 years. Revision rate was followed up over 13 years for a mean of 7.4 years post-surgery. The average Oxford score at one year was 43 with an average increase from pre-operation to 1 year post operation of 15. For the 7 patients with 10 year follow up average oxford score was 42 at 1 year, 43 at 5 years and 45 at 10 years. There were 5 reoperations. 2 for revision to total knee arthroplasty and 1 for an exchange of bearing due to wear. The other 2 were the addition of another UKR. For those requiring reoperation the average time was 8 years. Younger more active patients presenting with ACL deficiency causing instability and unicompartmental arthritis are a difficult group to manage. Combining UKR and ACL reconstruction has scant evidence in regard to long term follow up but is a viable option for this select group. This paper has one of the largest cohorts with a reasonable follow up averaging 7.4 years and a revision rate of 11 percent. Combined unilateral knee replacements and ACL reconstruction can be a successful operation for patients with ACL rupture causing instability and unicompartmental arthritis.
Approximately 20% of primary and revision Total Knee Arthroplasty (TKA) patients require multiple revisions, which are associated with poor survivorship, with worsening outcomes for subsequent revisions. For revision surgery, either endoprosthetic replacements or metaphyseal sleeves can be used for the repair, however, in cases of severe defects that are deemed “too severe” for reconstruction, endoprosthetic replacement of the affected area is recommended. However, endoprosthetic replacements have been associated with high complication rates (high incidence rates of prosthetic joint infection), while metaphyseal sleeves have a more acceptable complication profile and are therefore preferred. Despite this, no guidance exists as to the maximal limit of bone loss, which is acceptable for the use of metaphyseal sleeves to ensure sufficient axial and rotational stability. Therefore, this study assessed the effect of increasing bone loss on the primary stability of the metaphyseal sleeve in the proximal tibia to determine the maximal bone loss that retains axial and rotational stability comparable to a no defect control. to determine the pattern of bone loss and the average defect size that corresponds to the clinically defined defect sizes of small, medium and large defects, a series of pre-operative x-rays of patients with who underwent revision TKA were retrospectively analysed. Ten tibiae sawbones were used for the experiment. To prepare the bones, the joint surface was resected the typical resection depth required during a primary TKA (10mm). Each tibia was secured distally in a metal pot with perpendicular screws to ensure rotational and axial fixation to the testing machine. Based on X-ray findings, a fine guide wire was placed 5mm below the cut joint surface in the most medial region of the plateau. Core drills (15mm, 25mm and 35mm) corresponding to small, medium and large defects were passed over the guide wire allowing to act at the centre point, before the bone defect was created. The test was carried out on a control specimen with no defect, and subsequently on a Sawbone with a small, medium or large defect. Sleeves were inserted using the published operative technique, by trained individual using standard instruments supplied by the manufacturers. Standard axial pull-out (0 – 10mm) force and torque (0 – 30°) tests were carried out, recording the force (N) vs. displacement (mm) curves. A circular defect pattern was identified across all defects, with the centre of the defect located 5mm below the medial tibial base plate, and as medial as possible. Unlike with large defects, small and medium sized defects reduced the pull-out force and torque at the bone-implant interface, however, these reductions were not statistically significant when compared to no bony defect.Abstract
Methods
Results
Diagnosis of periprosthetic shoulder infections (PSI) is difficult as they are mostly caused by low-virulent bacteria and patients do not show typical infection signs, such as elevated blood markers, wound leakage, or red and swollen skin. Ultrasound-guided biopsies for culture may therefore be an alternative for mini-open biopsies as less costly and invasive method. The aim of this study was to determine the diagnostic value and reliability of ultrasound-guided biopsies for cultures alone and in combination polymerase chain reaction (PCR), and/or synovial markers for preoperative diagnosis of PSI in patients undergoing revision shoulder surgery. A prospective explorative diagnostic cohort study was performed including patients undergoing revision shoulder replacement surgery. A shoulder puncture was taken preoperatively before incision to collect synovial fluid for interleukin-6 (IL-6), calprotectin, WBC, polymorphonuclear cells determination. Prior to revision surgery, six ultrasound-guided synovial tissue biopsies were collected for culture and two additional for PCR analysis. Six routine care tissue biopsies were taken during revision surgery and served as reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV; primary outcome measure), and accuracy were calculated for ultrasound-guided biopsies, and synovial markers, and combinations of these.Aim
Method
Angular deformities of the distal femur can be corrected by opening, closing and neutral wedge techniques. Opening wedge (OW) and closing wedge (CW) are popular and well described in the literature. CW and OW techniques lead to leg length difference whereas the advantage of neutral wedge (NW) technique has several unique advantages. NW technique maintains limb length, wedge taken from the closing side is utilised on the opening side and since the angular correction is only half of the measured wedge on either side, translation of distal fragment is minimum. Leg lengths are not altered with this technique hence a useful technique in large deformities. We found no reports of clinical outcomes using NW technique. We present a technique of performing external fixator assisted NW correction of large valgus and varus deformities of distal femur and dual plating and discuss the results. We have treated 20 (22 limbs – 2 patients requiring staged bilateral corrections) patients for distal femoral varus and valgus deformities with CWDFO between 2019 and 2022. Out of these 4 patients (5 limbs) requiring large corrections of distal femoral angular deformities were treated with Neutral Wedge (NW) technique. 3 patients (four limbs) had distal femoral valgus deformity and one distal femoral varus deformity. Indication for NW technique is an angular deformity (varus or valgus of distal femur) requiring > 12 mm opening/closing wedge correction. We approached the closing side first and marked out the half of the calculated wedge with K – wires in a uniplanar fashion. Then an external fixator with two Schanz screws is applied on the opposite side, inserting the distal screw parallel to the articular surface and the proximal screw 6–7 cm proximal to the first pin and at right angles to the femoral shaft mechanical axis. Then the measured wedge is removed and carefully saved. External fixator is now used to close the wedge and over correct, creating an appropriate opening wedge on the opposite side. A Tomofix (Depuoy Synthes) plate is applied on the closing side with two screws proximal to osteotomy and two distally (to be completed later). Next the osteotomy on the opposite side is exposed, the graft is inserted. mLDFA is measured under image intensifier to confirm satisfactory correction. Closing wedge side fixation is then completed followed by fixation of opposite side with a Tomofix or a locking plate.Introduction
Materials & Methods
Neonatal motor development transitions from initially spontaneous to later increasingly complex voluntary movements. A delay in transitioning may indicate cerebral palsy (CP). The general movement optimality score (GMOS) evaluates infant movement variety and is used to diagnose CP, but depends on specialized physiotherapists, is time-consuming, and is subject to inter-observer differences. We hypothesised that an objective means of quantifying movements in young infants using motion tracking data may provide a more consistent early diagnosis of CP and reduce the burden on healthcare systems. This study assessed lower limb kinematic and muscle force variances during neonatal infant kicking movements, and determined that movement variances were associated with GMOS scores, and therefore CP. Electromagnetic motion tracking data (Polhemus) was collected from neonatal infants performing kicking movements (min 50° knee extension-flexion, <2 seconds) in the supine position over 7 minutes. Tracking data from lower limb anatomical landmarks (midfoot inferior, lateral malleolus, lateral knee epicondyle, ASIS, sacrum) were applied to subject-scaled musculoskeletal models (Gait2354_simbody, OpenSim). Inverse kinematics and static optimisation were applied to estimate lower limb kinematics (knee flexion, hip flexion, hip adduction) and muscle forces (quadriceps femoris, biceps femoris) for isolated kicks. Functional principal component analysis (fPCA) was carried out to reduce kicking kinematic and muscle force waveforms to PC scores capturing ‘modes’ of variance. GMOS scores (lower scores = reduced variety of movement) were collected in parallel with motion capture by a trained operator and specialised physiotherapist. Pearson's correlations were performed to assess if the standard deviation (SD) of kinematic and muscle force waveform PC scores, representing the intra-subject variance of movement or muscle activation, were associated with the GMOS scores.Abstract
Objectives
Methods
Obesity is a common in individuals undergoing arthroplasty, and the potential for weight loss with improved mobility may be expected by some. The aim of this study was 1. determine the proportion that achieved weight loss after hip or knee arthroplasty, and 2. examine the effect of obesity on patient reported outcomes (PROMS) and satisfaction with surgery. Participants underwent primary TKA or THA between July 2015 and December 2020 and consented to participation in a research database with baseline PROMS, including weight, BMI, Oxford Knee, or Hip Score, and EQ5D. Participants repeated PROMS at 12 months after surgery with additional questions regarding satisfaction with surgery. 3449 patients completed PROMS 1 year after arthroplasty with weight and BMI. There were 1810 THA and 1639 TKA procedures. The mean baseline BMI was higher in TKA (29.8, SD 5.2) compared to THA (27.7, SD 5.0), p=0.001. A higher proportion of TKA were classified as obese class 1 (29% TKA, 19% THA), obese class 2 (11% TKA and 6% THA), and obese class 3 (5% TKA and 2% THA), p=0.001. The mean weight loss after 1 year was 0.4kg and 0.9kg in obese THA subjects and TKA subjects respectively. In the obese >5kg weight loss was achieved in 13% of TKA and 7% of THA (p=0.001). Obese experienced equivalent improvement in Oxford scores, compared to non-obese subjects. Satisfaction with surgery was reported by 95% of THA and 91% of TKA subjects with no significant differences between BMI group grades (p=0.491 THA and p=0.473 TKA). Preoperative obesity was observed in 44% of TKA and 27% of THA subjects. In the obese only 1 in 10 subjects lost 5kg or more over 12 months. Obese patients experienced equivalent improvements in outcome after arthroplasty and rates of satisfaction with surgery to the non-obese.
Glutamate regulates the expression of apoptosis-related genes and triggers the apoptosis of fibroblasts in rotator cuff tendons. Subacromial bursitis is always accompanied by symptomatic rotator cuff tear (RCT). However, no study has been reported on the presence of glutamate in subacromial bursa and on its involvement of shoulder pain in patients who had RCT. The purposes of this study were to determine whether the glutamate expression in subacromial bursa is associated with the presence of RCT and with the severity of shoulder pain accompanying RCT. Subacromial bursal tissues were harvested from patients who underwent arthroscopic rotator cuff tendon repair or glenoid labral repair with intact rotator cuff tendon. Glutamate tissue concentrations were measured, using a glutamate assay kit. Expressions of glutamate and its receptors in subacromial bursae were histologically determined. The sizes of RCT were determined by arthroscopic findings, using the DeOrio and Cofield classification. The severity of shoulder pain was determined, using visual analog scale (VAS). Any associations between glutamate concentrations and the size of RCT were evaluated, using logistic regression analysis. The correlation between glutamate concentrations and the severity of pain was determined, using the Pearson correlation coefficient. Differences with a probability <0.05 were considered statistically significant. Glutamate concentrations showed significant differences between the torn tendon group and the intact tendon group (P = 0.009). Concentrations of glutamate significantly increased according to increases in tear size (P < 0.001). In histological studies, the expressions of glutamate and of its ionotropic and metabotropic receptors have been confirmed in subacromial bursa. Glutamate concentrations were significantly correlated with pain on VAS (Rho=0.56 and P =0.01). The expression of glutamate in subacromial bursa is significantly associated with the presence of RCT and significantly correlated with its accompanying shoulder pain.
ZrN-multilayer coating is clinically well established in total knee arthroplasty [1–3] and has demonstrated significant reduction in polyethylene wear and metal ion release [4,5]. The goal of our study was to analyze the biotribological behaviour of the ZrN-multilayer coating on a polished cobalt-chromium cemented hip stem. CoCr28Mo6 alloy hip stems with ZrN-multilayer coating (CoreHip®AS) were tested versus an un-coated version. In a worst-case-scenario the stems with ceramic heads have been tested in bovine serum in a severe cement interface debonding condition under a cyclic load of 3,875 N for 15 million cycles. After 1, 3, 5, 10 & 15 million cycles the surface texture was analysed by scanning-electron-microscopy (SEM) and energy-dispersive x-ray (EDX). Metal ion concentration of Co,Cr,Mo was measured by inductively coupled plasma mass spectroscopy (ICP-MS) after each test interval. Based on SEM/EDX analysis, it has been demonstrated that the ZrN-multilayer coating keeps his integrity over 15 million cycles of severe stem cemented interface debonding without any exposure of the CoCr28Mo6 substrate. The ZrN-multilayer coated polished cobalt-chromium cemented hip stem has shown a reduction of Co & Cr metal ion release by two orders of a magnitude, even under severe stem debonding and high interface micro-motion conditions. ZrN-multilayer coating on polished cobalt-chromium cemented hip stems might be a suitable option for further minimisation of Co & Cr metal ion release in total hip arthroplasty. Clinical evidence has to be proven during the next years.
An increased number of neutrophils (NEUs) has long been associated with infections in the knee joints; their contribution to knee osteoarthritis (KOA) pathophysiology remains largely unexplored. This study aimed to compare the phenotypic and functional characteristics of synovial fluid (SF)-derived NEUs in KOA and knee infection (INF). Flow cytometric analysis, protein level measurements (ELISA), NEU oxidative burst assays, detection of NEU phagocytosis (pHrodoTM Green Zymosan BiparticlesTM Conjugate for Phagocytosis), morphological analysis of the SF-derived/synovial tissue NEUs, and cultivation of human umbilical vein endothelial cells (HUVECs) using SF supernatant were used to characterise NEUs functionally/morphologically. Results: Compared with INF NEUs, KOA NEUs were characterised by a lower expression of CD11b, CD54 and CD64, a higher expression of CD62L, TLR2 and TLR4, and lower production of inflammatory mediators and proteases, except CCL2. Functionally, KOA NEUs displayed an increased production of radical oxygen species and phagocytic activity compared with INF NEUs. Morphologically, KOA and INF cells displayed different cell sizes and morphology, histological characteristics of the surrounding synovial tissues and influence on endothelial cells. KOA NEUs were further subdivided into two groups: SF containing <10% and SF with 10%–60% of NEUs. Analyses of two KOA NEU subgroups revealed that NEUs with SF <10% were characterised by 1) higher CD54, CD64, TLR2 and TLR4 expression on their surface; 2) higher concentrations of TNF-α, sTREM-1, VILIP-1, IL-1RA and MMP-9 in SFs. Our findings reveal a key role for NEUs in the pathophysiology of KOA, indicating that these cells are morphologically and functionally different from INF NEUs. Further studies should explore the mechanisms that contribute to the increased number of NEUs and their crosstalk with other immune cells in KOA. This study was supported by the Ministry of Health of the Czech Republic (NU20-06-00269; NU21-06-00370).
Osteoarthritis, the most common degenerative joint disease, significantly impairs life quality and labor capability of patients. Synovial inflammation, initiated by HMGB1 (High mobility group box 1)-induced activation of macrophage, precedes other pathological changes. As an upstream regulator of NF-κB (nuclear factor-kappa B) and MAPK (mitogen-activated protein kinase) signaling pathway, TAK1 (TGF-β activated kinase 1) participates in macrophage activation, while its function in osteoarthritis remains unveiled. This study aims to investigate the role of TAK1 in the pathogenesis of osteoarthritis via both in vitro and in vivo approaches. We performed immunohistochemical staining for TAK1 in synovial tissue, both in osteoarthritis patients and healthy control. Besides, immunofluorescence staining for F4/80 as macrophage marker and TAK1 were conducted as well. TAK1 expression was examined in RAW264.7 macrophages stimulated by HMGB1 via qPCR (Quantitative polymerase chain reaction) and Western blotting, and the effect of TAK1 inhibitor (5z-7 oxozeaenol) on TNF-α production was evaluated by immunofluorescence staining. Further, we explored the influence of intra-articular shRNA (short hairpin RNA) targeting TAK1 on collagenase-induced osteoarthritis in mice. Immunohistochemical staining confirmed significant elevation of TAK1 in osteoarthritic synovium, and immunofluorescence staining suggested macrophages as predominant residence of TAK1. In HMGB1-stimulated RAW264.7 macrophages, TAK1 expression was up-regulated both in mRNA and protein level. Besides, TAK1 inhibitor significantly impairs the production of TNF-α by macrophages upon HMGB1 stimulation. Moreover, intra-articular injection of lentivirus loaded with shRNA targeting TAK1 (sh-TAK1) reduced peri-articular osteophyte formation in collagenase-induced osteoarthritis in mice. TAK1 exerts a potent role in the pathogenesis of osteoarthritis by mediating the activation of macrophages.
Energy storing tendons such as the human Achilles and equine superficial digital flexor tendon (SDFT) are prone to age-related injury. Tendons have poor healing capacity and a lack of effective treatments can lead to ongoing pain, reduced function and re-injury. It is therefore important to identify the mechanisms underpinning age-related tendinous changes in order to develop more effective treatments. Our recent single cell sequencing data has shown that tendon cell populations have extensive heterogeneity and cells housed in the tendon interfascicular matrix (IFM) are preferentially affected by ageing. There is, however, a lack of established surface markers for cell populations in tendon, limiting the capacity to isolate distinct cell populations and study their contribution to age-related tendon degeneration. Here, we investigate the presence of the cell surface proteins MET proto-oncogene (MET), integrin subunit alpha 10 (ITGA10), fibroblast activation protein alpha (FAP) and platelet derived growth factor receptor alpha (PDGFRA) in the equine SDFT cell populations and their co-localisation with known markers. Using Western blot we validated the specificity of selected antibodies in equine tissue before performing immunohistochemistry to establish the location of the respective proteins in the SDFT. We subsequently used double labelling immunofluorescence with the established mural cell marker desmin (DES) to distinguish between tenocyte and mural cell populations. In situ, MET, ITGA10, and FAP presence was found in cells throughout the tendon whereas PDGFRA was present in cells within the IFM. Double labelling immunofluorescence with the mural cell marker DES showed lack of co-localisation between PDGFRA and DES suggesting PDGFRA is labelling an IFM cell population distinct from those associated with blood vessels. PDGFRA is a promising target for the specific cell sorting of IFM-localised tenocytes, enabling their isolation and subsequent characterisation.
