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.

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An increasing number of patients with hepatitis B virus (HBV) infection are progressing in age and are undergoing total joint arthroplasty (TJA) surgery in China. Less attention is provided to the special populations. This study aimed to evaluate the effect of HBV on TJAs. We retrospectively reviewed all patients who met the inclusion of undergoing elective primary hip and knee arthroplasties from 2013– 2016. Non-hepatitis B cohort was built to match the case cohort to identify whether HBV infection was a risk factor associated with postoperative complications. A total number of 197 patients who underwent primary TJAs were involved in the study, including 49 patients with hepatitis B and 147 non-hepatitis B subjects. Among all the patients with TJAs, we obtained a 5.5% HBV infection rate for the first time. Compared with patients without hepatitis B, patients with hepatitis B had higher rates (P < 0.01) of total complications (10.2% compared to 4.7%), surgery-related complications (6.1% compared to 3.4%), and general medical complications (4.1% compared to 1.3%) than the non-hepatitis B group. Patients with hepatitis B infection had a 21% increased risk (95% CI, 0.97–1.46; p < 0.01) of total complication compared with non-hepatitis B group. Similar results were obtained for medical and surgical complications. HBV infection had a 31% increased risk (95% CI, 1.02–1.62; p < 0.01) for medical complication and 18% risk (95% CI, 0.95–1.42; p < 0.01) for surgical complication. In the subgroup analysis, no difference was found between the surgical methods and sex, whereas a significant difference of CRP change level (P < 0.01) was found between HBV group and the matched group in the clinical laboratory values. This is the first study of patients with hepatitis B undergoing primary THA or TKA and demonstrates an increased risk of multiple perioperative complications in a Chinese population. In consideration of the large population of HBV infection in China, more attention should be provided to patients with HBV infection who need to undergo TJAs.