Activation of NRF2 by celastrol increases antioxidant functions and prevents the progression of osteoarthritis in mice.

Excessive oxidative stress impairs cartilage matrix metabolism balance, significantly contributing to osteoarthritis (OA) development. Celastrol (CSL), a drug derived from Tripterygium wilfordii, has recognized applications in the treatment of cancer and immune system disorders, yet its antioxidative stress mechanisms in OA remain underexplored. This study aimed to substantiate CSL's chondroprotective effects and unravel its underlying mechanisms. We investigated CSL's impact on chondrocytes under both normal and inflammatory conditions. In vitro, CSL mitigated interleukin (IL)-1ß-induced activation of proteinases and promoted cartilage extracellular matrix (ECM) synthesis. In vivo, intra-articular injection of CSL ameliorated cartilage degeneration and mitigated subchondral bone lesions in OA mice. Mechanistically, it was found that inhibiting nuclear factor erythroid 2-related factor 2 (NRF2) abrogated CSL-mediated antioxidative functions and exacerbated the progression of OA. This study is the first to elucidate the role of CSL in the treatment of OA through the activation of NRF2, offering a novel therapeutic avenue for arthritis therapy.

A retrospective study on the efficacy and safety of bone cement in the treatment of endplate fractures.

Background: Endplate fractures is an important factor affecting the curative effect of percutaneous kyphoplasty for spinal fracture. The purpose of this study is to investigate the effect of sealing endplate fracture with bone cement on minimally invasive treatment of spinal fracture. Methods: A total of 98 patients with osteoporotic vertebral fractures combined with endplate fractures treated with bone cement surgery in our hospital were retrospectively analyzed. They were grouped according to whether bone cement was involved in the endplate fractures. Group A: bone cement was not only distributed in the fractured vertebral body, but also dispersed into the endplate fractures. Group B: bone cement was confined to the fractured vertebra but did not diffuse into the cracks of the endplate. The basic information, imaging changes of the fractured vertebral body, VAS score, ODI score, bone cement distribution and postoperative complications of the two groups were analyzed and compared. Results: The height of the injured vertebra and the kyphotic Cobb angle in the two groups were significantly improved after surgery, but the anterior height of the vertebra in group B was lower than that in group A and the kyphotic Cobb angle was higher than that in group A at the last follow-up (P < 0.05). VAS score and ODI score in 2 groups were significantly improved after operation (P < 0.05), but the VAS score and ODI score in group A were lower than those in group B at the last follow-up (P < 0.05). The incidence of bone cement leakage and adjacent vertebral fracture in group A was higher than that in group B (P < 0.05). Conclusion: Diffusion of bone cement into the cracks of the endplate may also restore and maintain the height of the injured vertebra, relieve pain and restore lumbar function. However, diffusion of bone cement into the cracks of the endplate can increase the incidence of cement leakage and adjacent vertebral fractures.

Study on the influence of balloon dilation mode on the intravertebral cleft of osteoporotic fracture.

BACKGROUND: Intravertebral cleft is common in osteoporotic vertebral compression fracture, and the bone sclerosis around the fissure brings difficulties to the surgical treatment. It is not known whether the balloon dilatation mode of percutaneous kyphoplasty affects the distribution of bone cement in the fracture vertebral body and further affects the surgical effect. The purpose of this study was to discuss the effect of balloon dilatation mode on percutaneous kyphoplasty in the treatment of osteoporotic vertebral fractures with intravertebral cleft. METHODS: According to the inclusion criteria and exclusion criteria, a retrospective analysis of patients with osteoporotic vertebral fracture combined with intravertebral cleft treated by percutaneous kyphoplasty in our hospital was conducted. All patients were divided into two groups based on way of balloon dilation. The mode of balloon dilatation, imaging changes of vertebral body, VAS score, ODI score, bone cement distribution and postoperative complications were analyzed. RESULTS: A total of 96 patients with osteoporotic vertebral fracture combined with intravertebral cleft were included in the study, including 51 patients treated with single balloon bilateral alternating dilatation technique and 45 patients treated with double balloon bilateral dilatation technique. The vertebral height, Cobb's angle of kyphosis, VAS score and ODI score were significantly improved in both groups after operation (P < 0.05). The postoperative vertebral height and Cobb's angle of kyphosis in the double balloon bilateral dilatation group were better than those in single balloon bilateral alternating dilatation group (P < 0.05). The distribution of bone cement in the single balloon bilateral alternating dilatation group was more inclined to insert filling, while the double balloon bilateral dilatation group was more inclined to fissure filling. The VAS score and ODI score at the final follow-up in the single balloon bilateral alternating dilatation group were lower than those in the double balloon bilateral dilatation group (P < 0.05). CONCLUSION: Double balloon bilateral dilatation technique can better restore the injured vertebral height in patients with osteoporotic vertebral fracture combined with intravertebral cleft. However, the distribution of injured vertebral cement in patients with single balloon bilateral alternating dilatation technique is more likely to be inserted and filled, and the long-term analgesia and lumbar function of patients are better.

Heparin-Induced Thrombocytopenia Caused by Preventive Anticoagulation After Femoral Intertrochanteric Fracture Surgery: a Case Report.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a severe complication caused by heparin. It is characterized by occult onset and missed diagnosis. Misdiagnosis easily occurs. METHODS: This paper reported an 85-year-old woman with an intertrochanteric fracture of the femur which was treated with low molecular weight heparin (LMWH) and fondaparinux sodium to prevent venous thrombosis. Then, the patient developed HIT. This is the first case report of HIT induced by LMWH and fondaparinux in a patient with a hip fracture. This case highlights the severity of HIT in elderly patients with hip fractures using LMWH and fondaparinux and the need for platelet monitoring in these patients. RESULTS: LMWH was ceased in this HIT-confirmed patient, and non-heparin treatment was begun instead. Apixaban was given twice daily for therapeutic anticoagulation therapy. In the end, the platelet levels gradually returned to normal. CONCLUSIONS: We should pay more attention to HIT and platelets during the perioperative period of orthopedic surgery, especially in elderly patients. Once the disease is confirmed, it is necessary to stop heparin-related drugs immediately and administer oral anticoagulants instead.

Effect of water-soluble chitosan on the osteoblast function in MC3T3-E1 cells.

In the present study, water-soluble chitosan (WSC) was prepared by hydrolysis of chitosan with commercial α-amylase, and the effect of WSC on osteoblast function, i.e. alkaline phosphatase activity (ALP), cell viability, mineralization, and reactive oxygen species (ROS) in osteoblastic MC3T3-E1 cells was investigated. Osteoblastic MC3T3-E1 cells were cultured in various concentrations of WSC solutions (1-5 mg/mL) for designated time and then the ALP, cell viability, mineralization, and ROS in the cells were evaluated. Treatments of osteoblastic with WSC caused a significant increase in ALP, cell viability, and mineralization in osteoblastic MC3T3-E1 cells. Moreover, treatments of osteoblastic with WSC decreased ROS level in osteoblastic MC3T3-E1 cells. The results demonstrate that the WSC may reduce or prevent osteoblasts degeneration through antioxidant activity.