Engineered adipose-derived stem cells with IGF-1-modified mRNA ameliorates osteoarthritis development

Background Osteoarthritis (OA), a prevalent degenerative disease characterized by degradation of extracellular matrix (ECM), still lacks effective disease-modifying therapy. Mesenchymal stem cells (MSCs) transplantation has been regarded as the most promising approach for OA treatment while engrafting cells alone might not be adequate for effective regeneration. Genetic modification has been used to optimize MSC-based therapy; however, there are still significant limitations that prevent the clinical translation of this therapy including low efficacy and safety concerns. Recently, chemically modified mRNA (modRNA) represents a promising alternative for the gene-enhanced MSC therapy. In this regard, we hypothesized that adipose derived stem cells (ADSCs) engineered with modRNA encoding insulin-like growth factor 1 (IGF-1) were superior to native ADSCs on ameliorating OA development. Methods Mouse ADSCs were acquired from adipose tissue and transfected with modRNAs. First, the kinetics and efficacy of modRNA-mediated gene transfer in mouse ADSCs were analyzed in vitro. Next, we applied an indirect co-culture system to analyze the pro-anabolic potential of IGF-1 modRNA engineered ADSCs (named as IGF-1-ADSCs) on chondrocytes. Finally, we evaluated the cell retention and chondroprotective effect of IGF-1-ADSCs in vivo using fluorescent labeling, histology and immunohistochemistry. Results modRNA transfected mouse ADSCs with high efficiency (85 ± 5%) and the IGF-1 modRNA-transfected ADSCs facilitated burst-like production of bio-functional IGF-1 protein. In vitro, IGF-1-ADSCs induced increased anabolic markers expression of chondrocytes in inflammation environment compared to untreated ADSCs. In a murine OA model, histological and immunohistochemical analysis of knee joints harvested at 4 weeks and 8 weeks after OA induction suggested IGF-1-ADSCs had superior therapeutic effect over native ADSCs demonstrated by lower histological OARSI score and decreased loss of cartilage ECM. Conclusions These findings collectively supported the therapeutic potential of IGF-1-ADSCs for clinical OA management and cartilage repair.

RGB-D-Based Method for Measuring the Angular Range of Hip and Knee Joints during Home Care Rehabilitation

Home-based rehabilitation is becoming a gold standard for patient who have undergone knee arthroplasty or full knee replacement, as it helps healthcare costs to be minimized. Nevertheless, there is a chance of increasing adverse health effects in case of home care, primarily due to the patients’ lack of motivation and the doctors’ difficulty in carrying out rigorous supervision. The development of devices to assess the efficient recovery of the operated joint is highly valued both for the patient, who feels encouraged to perform the proper number of activities, and for the doctor, who can track him/her remotely. Accordingly, this paper introduces an interactive approach to angular range calculation of hip and knee joints based on the use of low-cost devices which can be operated at home. First, the patient’s body posture is estimated using a 2D acquisition method. Subsequently, the 3D posture is evaluated by using the depth information coming from an RGB-D sensor. Preliminary results show that the proposed method effectively overcomes many limitations by fusing the results obtained by the state-of-the-art robust 2D pose estimation algorithms with the 3D data of depth cameras by allowing the patient to be correctly tracked during rehabilitation exercises.

ER Stress in ERp57 Knockout Knee Joint Chondrocytes Induces Osteoarthritic Cartilage Degradation and Osteophyte Formation

Ageing or obesity are risk factors for protein aggregation in the endoplasmic reticulum (ER) of chondrocytes. This condition is called ER stress and leads to induction of the unfolded protein response (UPR), which, depending on the stress level, restores normal cell function or initiates apoptotic cell death. Here the role of ER stress in knee osteoarthritis (OA) was evaluated. It was first tested in vitro and in vivo whether a knockout (KO) of the protein disulfide isomerase ERp57 in chondrocytes induces sufficient ER stress for such analyses. ER stress in ERp57 KO chondrocytes was confirmed by immunofluorescence, immunohistochemistry, and transmission electron microscopy. Knee joints of wildtype (WT) and cartilage-specific ERp57 KO mice (ERp57 cKO) were analyzed by indentation-type atomic force microscopy (IT-AFM), toluidine blue, and immunofluorescence/-histochemical staining. Apoptotic cell death was investigated by a TUNEL assay. Additionally, OA was induced via forced exercise on a treadmill. ER stress in chondrocytes resulted in a reduced compressive stiffness of knee cartilage. With ER stress, 18-month-old mice developed osteoarthritic cartilage degeneration with osteophyte formation in knee joints. These degenerative changes were preceded by apoptotic death in articular chondrocytes. Young mice were not susceptible to OA, even when subjected to forced exercise. This study demonstrates that ER stress induces the development of age-related knee osteoarthritis owing to a decreased protective function of the UPR in chondrocytes with increasing age, while apoptosis increases. Therefore, inhibition of ER stress appears to be an attractive therapeutic target for OA.

High-Resolution Simultaneous Multi-Slice Accelerated Turbo Spin-Echo Musculoskeletal Imaging: A Head-to-Head Comparison With Routine Turbo Spin-Echo Imaging

Background/Aim: The turbo spin-echo (TSE) sequence is widely used for musculoskeletal (MSK) imaging; however, its acquisition speed is limited and can be easily affected by motion artifacts. We aimed to evaluate whether the use of a simultaneous multi-slice TSE (SMS-TSE) sequence can accelerate MSK imaging while maintaining image quality when compared with the routine TSE sequence.Methods: We prospectively enrolled 71 patients [mean age, 37.43 ± 12.56 (range, 20–67) years], including 37 men and 34 women, to undergo TSE and SMS sequences. The total scanning times for the wrist, ankle and knee joint with routine sequence were 14.92, 13.97, and 13.48 min, respectively. For the SMS-TSE sequence, they were 7.52, 7.20, and 6.87 min. Quantitative parameters, including the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), were measured. Three experienced MSK imaging radiologists qualitatively evaluated the image quality of bone texture, cartilage, tendons, ligament, meniscus, and artifact using a 5-point evaluation system, and the diagnostic performance of the SMS-TSE sequences was evaluated.Results: Compared with the routine TSE sequences, the scanning time was lower by 49.60, 48.46, and 49.04% using SMS-TSE sequences for the wrist, ankle, and knee joints, respectively. For the SNR comparison, the SMS-TSE sequences were significantly higher than the routine TSE sequence for wrist (except for Axial-T2WI-FS), ankle, and knee joint MR imaging (all p < 0.05), but no statistical significance was obtained for the CNR measurement (all p > 0.05, except for Sag-PDWI-FS in ankle joint). For the wrist joint, the diagnostic sensitivity, specificity, and accuracy were 88.24, 100, and 92%. For the ankle joint, they were 100, 75, and 93.33%. For the knee joint, they were 87.50, 85.71, and 87.10%.Conclusion: The use of the SMS-TSE sequence in the wrist, ankle, and knee joints can significantly reduce the scanning time and show similar image quality when compared with the routine TSE sequence.

Primary hypertrophic osteoarthropathy and bilateral transient lateral patellar dislocation in an adolescent

This case report is of the index case of bilateral transient patellar dislocation in a patient with primary hypertrophic osteoarthropathy. Primary hypertrophic osteoarthropathy is a rare complex disorder with variable presentation and thus frequently delayed diagnosis. Notably this disease has multiple skeletal manifestations and, of relevance to this case, a proportion of patients suffer from osteitis. Our patient had serial imaging of the knee joints demonstrating osteitis and associated alteration of the femoral trochlea morphology, predisposing to bilateral transient lateral patellar dislocation. The patient’s clinical presentation, diagnosis and management are discussed. Classification of the disease and its diagnostic parameters are summarised along with key imaging features amongst various imaging modalities.

Anthropometric Analysis of Human Knee Joint in Indian Population

Background: It is well understood that distal femoral and proximal tibia scale is lower in case of the Asian than that of their western counterparts. Because of the Asian population's comparatively smaller structure and stature, many surgeons claim that imported implants may not be well fitted for Asian origin patients, mainly based on Western morphometry. It is very likely that an overweight section will be used in many Asian centres in most operations, resulting in low results of the procedure of the implant. For joint substitution of distal femur, careful positioning of fitted implants as well as balancing of underlying soft tissues is important. It is also important to use incredibly complex surgical procedures. To retain its usual functional motion spectrum, use of a suitable femoral part dimension is necessary. Furthermore, owing to a discrepancy between the size of the prosthesis and the bone, there could be a host of serious issues. Objectives: To calculate the anthropometric distal femur parameter and determine the distal femur variations on the right and left side of the morph metric measurement and to evaluate dimension of current TKA as related to Indian population. Methodology: This study included visiting the out patients Department of Orthopedics, at AVBRH in the age group 30-50 year during the period of June-2020 to April-2023 with sample size of 50 patients. Detailed history and clinical review will be taken, including age, sex, socio-economic background, type of employment. In all patients involved in the study in Orthopedic OPD, thorough radiological assessment of all the knee joints will be performed. The radiological test and various anthropometrics will include knee joint Simple X-ray and CT-Scan. Expected Results: We expect that from our results, anthropometric measurements of Indian population may differ from other literatures.

Advanced Physiotherapy of Supracondylar Femur Fracture with Implant In situ: A Case Report

Patient main concerns were restriction of movements of right knee and pus discharge from wound over right knee. In this case, the main clinical findings were a substantial loss in range of motion at right knee joints. There was also fixed flexion deformity seen over right knee. Diagnosis of the case was non united operated infected case of supracondylar femur fracture right side with implant in situ. In these types of circumstances, therapeutic approaches have been demonstrated to be useful. A 35-year-old male visited the orthopaedics who referred department of physiotherapy with complaints of restriction of movement of right knee and pus discharge from wound over right knee. Patient was examine in standing and supine position .On inspection, patient keeps right hip in flexion, knee in flexion patella pointing upwards and foot in equinus. According to the research, starting weight-bearing too soon can lead to failure of implant and mal-union. Supracondylar femoral fracture is a challenging condition to deal with and is associated with many secondary complications. An important role is played by physiotherapist in rehabilitation and supracondylar femur fracture management.

Peculiarities of knee replacement in patients with rheumatoid arthritis

Introduction. Rheumatoid arthritis (RA), as a steadily progressive disease leading to joint destruction and functional instability of the knee joints, often requires orthopedic correction.The aim. Of the review was to analyze the surgery strategy and technical features of knee arthroplasty and replacement in patients with RA.Basic provisions. RA is characterized by a number of abnormalities not only due to erosive arthritis and active persistent synovitis, but also caused by a decrease in bone mineral density, damage to the periarticular structures and patella, the formation of bone defects, as well as a high risk of postoperative complications. All these factors should be taken into account while choosing relevant surgical treatment and knee replacement technique. The article presents the optimal approaches for performing knee replacement in RA patients, taking into account the peculiarities of the existing structural and functional disorders.Conclusion. TEC in patients with RA requires a personalized approach based on evaluation of disease-associated risk factors affecting the results of orthopedic correction and the likelihood of complications.

Meniscus Injury and its Surgical Treatment Does not Increase Initial Whole Knee Joint Friction

While it is generally accepted that traumatic meniscus pathologies lead to degenerative articular cartilage changes in the mid-to long-term and consecutively to post-traumatic osteoarthritis (PTOA), very little is known about how such injuries initiate tribological changes within the knee and their possible impact on PTOA acceleration. Therefore, the aim of this study was to investigate the influence of three different medial meniscus states (intact, posterior root tear, total meniscectomy) on the initial whole knee joint friction. Six ovine knee joints were tested in a passive pendulum friction testing device under an axial load of 250 N and an initial deflection of 12°, representing swing phase conditions, and under an axial load of 1000 N and an initial deflection of 5°, simulating stance phase conditions. To additionally consider the influence of the time-dependent viscoelastic nature of the knee joint soft tissues on whole joint friction, the tests were performed twice, directly following load application and after 20 min creep loading of either 250 N or 1000 N axial load. On the basis of a three-dimensional joint kinematic analysis, the energy loss during the passive joint motion was analyzed, which allowed considerations on frictional and damping processes within the joint. The so-called “whole knee joint” friction was evaluated using the boundary friction model from Stanton and a viscous friction model from Crisco et al., both analyzing the passive joint flexion-extension motion in the sagittal plane. Significantly lower friction coefficients were observed in the simulated swing phase after meniscectomy (p < 0.05) compared to the intact state. No initial whole joint friction differences between the three meniscus states (p > 0.05) were found under stance phase conditions. Soft tissue creeping significantly increased all the determined friction coefficients (p < 0.05) after resting under load for 20 min. The exponential decay function of the viscous friction model provided a better fit (R2∼0.99) to the decaying flexion-extension data than the linear decay function of the boundary friction model (R2∼0.60). In conclusion, this tribological in vitro study on ovine knee joints indicated that neither a simulated posterior medial meniscus root tear nor the removal of the medial meniscus resulted in an initially increased whole joint friction.