Tendinopathy is one of the most common orthopaedic pathological conditions characterized by tendon degenerative changes. Excessive mechanical loading is considered as a major causative factor in the development of tendinopathy, but the mechanisms of pathogenesis remain unclear. High mobility group box-1 (HMGB1), a potent inflammatory mediator when released into the matrix, has been identified in the early stage tendinopathy patients. Since the release and contribution of HMGB1 in tendinopathy development due to mechanical overloading is unknown, we investigated the role of HMGB1 in tendinopathy using a mouse intensive treadmill running (ITR) model and injection of glycyrrhizin (GL), a specific inhibitor of HMGB1. A total of 48 mice were divided into four groups, Cage Control group: The animals were allowed to move freely in their cage, GL group: The animals were received daily IP injection of GL (50 mg/kg body weight) for 24 weeks, ITR group: The animals ran on treadmill at 15 meters/min for three h/ day, five days a week for 12 or 24 weeks, GL+ITR group: The animals ran the same protocol as that of ITR group plus daily IP injection of GL for 12 or 24 weeks. Six mice/group were sacrificed at 12 or 24 weeks and the Achilles and patellar tendon tissues were harvested and used for histochemical staining and immunostaining. Mechanical overloading induced HMGB1 released from the cell nuclei to the matrix (Fig. 1a, b) caused tendon inflammation (Fig. 1c, d) and led to tendon degenerative changes (Fig. 1e-j). After 12 weeks of ITR, the tendon tissue near the bone insertion site showed typical tendinopathic changes in cell shape, accumulation of glycosaminoglycans (GAG) (Fig. 1e, f), and increase in SOX-9 staining (Fig. 1g-j). After 24 weeks ITR, the distal site of Achilles tendon showed considerable changes in cell shape (Fig. 2A, g, arrows), which is round compared to more elongated in the control and GL groups (Fig. 2A, e, f). However, daily treatment with GL prior to ITR blocked the cell shape change (Fig. 2A, h) and, ITR induced extensive GAG accumulation in ITR group (Fig. 2B, bottom panel). Furthermore, GL inhibited ITR-induced expression of chondrogenic markers (SOX-9 and collagen II) in the tendons (Fig. 3). Our results showed that mechanical overloading-induced HMGB1 plays a critical role in the development of tendinopathy by initiating tendon inflammation and eventual degeneration characterized by the presence of chondrocyte-like cells, accumulation of proteoglycans, high levels of collagen type II production, and chondrogenic marker SOX-9 expression. These results provide the first evidence for the role of HMGB1 as a therapeutic target to prevent tendinopathy before its onset and block further development at its early inflammation stages. The inhibition of tendinopathy development by GL administration in this study also suggests the putative therapeutic potential of this natural triterpene that is already in clinical use to treat other inflammation-related diseases. For any figures or tables, please contact authors directly

INTRODUCTION. Mechanical overloading of the knee can occur during activities of daily living such as stair climbing, jogging, etc. In this finite element study we aim to investigate which parameters could detrimentally influence peri-implant bone in the tibial reconstructed knee. Bone quality and patient variables are potential factors influencing knee overloading (Zimmerman 2016). METHODS. Finite element (FE) models of post-mortem retrieved tibial specimens (n=7) from a previous study (Zimmerman 2016) were created using image segmentation (Mimics Materialise v14) of CT scan data (0.6 mm voxel resolution). Tibial tray and polyethylene inserts were recreated from CT data and measurements of the specimens (Solidworks 2015). Specimens with varying implant geometry (keel/pegged) were chosen for this study. A cohesive layer between bone and cement was included to simulate the behavior of the bone–cement interface using experimentally obtained values. The FE models predict plasticity of bone according to Keyak (2005). Models were loaded to 10 body weight (BW) and then reduced to 1 BW to mimic experimental measurements. Axial FE bone strains at 1 BW were compared with experimental Digital Image Correlation (DIC) bone strains on cut sections of the specimens. After validation of the FE models using strain data, models were rotated and translated to the coordinate system defined in Bergmann (2014). Four loading cases were chosen – walking, descending stairs, sitting down and jogging. Element strains were written to file for post-processing. The bone in all FE models was divided into regions of equal thickness (10 mm) for comparison of strains. RESULTS. Results are shown for two specimens at present. Strain-maps of the specimen cut section compare reasonably well with FE cutting-plane strains. The FE models however show some regions of high strain in certain locations which do not correspond with the experimental results (Figure 1). Plasticity predicted by the models at 10 BW is shown in Figure 2. Median bone strains for two loading cases are shown as a function of distance below the tibial tray in Figure 3. This figure shows that specimen 1 is less likely to be overloaded during jogging when compared with specimen 2. Both specimens remain below the 7300 με threshold for compressive yield. DISCUSSION. Using functioning knee replacement tibial specimens, we study which factors influence bone overloading. Validation using DIC strain measurements is challenging due to the large plasticity regions predicted by the material model used here. The present results were obtained using plasticity relationships from Keyak (2005) for the proximal femur. To further improve on our results, plasticity-bone density relationships for the proximal tibia (Keyak 1996) will be included. Proximal tibial bone has been shown to be stiffer than femoral bone (Morgan 2003). Despite these limitations, FE models provide valuable information on the risk of overloading during daily living activities. The study will be expanded to include an analysis of implant geometry, bone quality and other loading cases. For any figures or tables, please contact the authors directly

The cause of elbow tendinosis is most likely a combination of mechanical overloading and abnormal microvascular responses. Numerous methods of treatment have been advocated. In this study, we evaluated the use of platelet-rich plasma (PRP) as a treatment for resistant epicondylitis. The rationale for using platelets is that they participate predominantly in the early inflammation phases and degranulation. They constitute a reservoir of critical growth factors and cytokines which when placed directly into the damaged tissue, may govern and regulate the tissue healing process. We looked at 25 patients (19 with lateral and 6 with medial) who failed to improve after physiotherapy, cortisone injections and application of epicondylar clasps and assessed the efficacy of platelet-rich plasma injections using Gravitational platelet separation system (GPS). The cohort of patients included over a period of three years had physiotherapy, stretches, epicondylar clasp and an average of 2.9steroid injections (1–6) before having a PRP injection. The mean patient age was 43 years ranging between 24 and 54. There were 11 men and 14 women. The study included 19 patients with lateral epicondylitis and 6 patients with symptoms on the medial side. The ratio between dominant and nondominant side was according to the literature: 76%. The quick DASH scores imroved by 14% on an average in the first 3 months and further 26% in the following 9 months. 4 patients needed reintervention, 3 lateral and 1 medial and had surgical release between 6 and 12 months. 2 of them had reinjections before surgery. No local infections except mild inflammation and no systemic effects were noted. Within the limitations of being a case series and limited follow-up PRP injections provided a safe and progressive benefit over a period of 1 year in refractory cases, providing a good nonoperative alternative