Four-Octyl Itaconate Protects Chondrocytes against H2O2-Induced Oxidative Injury and Attenuates Osteoarthritis Progression by Activating Nrf2 Signaling.

Nrf2 is a critical regulator of the antioxidant defense systems in cellular protection. Emerging evidence has shown that four-octyl itaconate (OI) activates Nrf2 cascade. In this study, the chondroprotective effects of OI on H2O2-stimulated chondrocytes and DMM-induced osteoarthritis (OA) progression were investigated. In primary murine chondrocytes, OI interrupted the binding of Keap1 and Nrf2, leading to accumulation and nuclear translocation of Nrf2 protein, as well as transcription and expression of Nrf2-dependent genes, such as HO-1, NQO1, and GCLC. Furthermore, OI inhibited cell death and apoptosis, as well as H2O2-stimulated ROS generation, lipid peroxidation, superoxide accumulation, and mitochondrial depolarization in chondrocytes, which were abolished by the silence or depletion of Nrf2. In addition, in vivo experiments revealed the therapeutic effects of OI on OA progression in a DMM mouse model. Collectively, these results suggested that OI might serve as a potential treatment for OA progression.

Capsular Healing in Interportal and Periportal Capsulotomy Methods of Hip Arthroscopy.

OBJECTIVE: To evaluate the midterm outcomes and the capsular healing in patients who had interportal capsulotomy versus periportal capsulotomy of hip arthroscopy. METHODS: Retrospectively reviewed 33 patients with labral tear received hip arthroscopy, with an average age of 41 (27-67) years, including 13 cases of Cam deformity and three cases of Pincer deformity. All patients had positive sign of flexion adduction internal rotation or flexion abduction external rotation. With MRI and radiographic (CT, X plain) imageological examination. MRI showed that all patients had labral tear. Radiographic finding (CT, X plain) showed the pathological changes of acetabular and femoral neck osteophyte. One group with 23 patients were treated with periportal capsulotomy. Another group with 10 patients were treated with interportal capsulotomy. All patients did not close the capsule. Clinical outcomes were measured with the Hip Outcome Score Activities of Daily Living (HOS-ADL) and the modified Harris Hip Score (mHHS), patient satisfaction measured with visual analogue scale (VAS). The healing of the capsule was evaluated by MRI. MRI showed continuous capsular indicated healing, discontinuous capsular indicated unhealing. Postoperatively 6 months, mHHS and HOS-ADL were obtained. Randomized controlled trials were used in this study for analysis. RESULTS: All patients were followed up with average time of 9.3 months(3-29 months). The postoperative symptoms were obviously relieved, the VAS decreased from (4.9 ± 0.6) to (1.2 ± 0.2) after 3 months postoperative. Follow up 6 months post-operation, patients in the interportal group, the mHHS and HOS-ADL scores improvement were respectively 69.4 ± 9.3 & 70 ± 8.8 pre-operation, and 92.5 ± 5.0 & 86.6 ± 5.4 post-operation (P < 0.05); Patients in the periportal group, the mHHS and HOS-ADL scores improvement were respectively 69.9 ± 15.8, 68.1 ± 15.0 pre-operation, and 90.1 ± 9.3 & 86.7 ± 7.9 post-operation (P < 0.05).The differences were statistically significant. Six months after operation, MRI showed that 23 patients with periportal capsulotomy, the capsule have healed, without other complications. Three of the ten patients with interportal capsulotomy were healed and seven were not. CONCLUSION: Interportal and periportal capsulotomy had good outcomes. The technique of periportal capsulotomy had little damage to the joint capsule. Although the capsule did not close, the capsule healed well in postoperative follow-up. The nonunion rate of the joint capsule was high in the interportal capsulotomy without close the capsule.

Increased Runx2 expression associated with enhanced Wnt signaling in PDLLA internal fixation for fracture treatment.

Poly-D-L lactide (PDLLA) biodegradable implants to heal fractures are widely applied in orthopedic surgeries. However, whether the process of fracture healing is regulated differently when PDLLA is used compared with traditional metal materials remains unclear. Runt-related transcription factor 2 (Runx2) and canonical Wnt signaling are essential and may interact reciprocally in the regulation of osteogenesis during bone repair. In the present study, a rat femoral open osteotomy model was used to compare the curative efficacy of a PDLLA rod and Kirschner wire under intramedullary fixation for fracture treatment. The dynamic expression of Runx2 and key components of the canonical Wnt signaling in callus tissue during fracture healing was also investigated. The results of the current study indicate that at weeks 4 and 6 following fixation, the callus bone structural parameters of microCT were significantly improved by PDLLA rod compared to that of Kirschner wire. In addition, at weeks 4 and 6 after fixation, the protein and mRNA expression of Runx2 and the positive regulators of canonical Wnt signaling, such as Wnts and ß-catenin, were significantly increased. However, the protein and mRNA expression levels of the negative regulators of canonical Wnt signaling, such as glycogen synthase kinase-3ß, were significantly decreased in callus tissue when treated with PDLLA rod compared with Kirschner wire. Collectively, these data indicate that compared to the traditional metal material, using PDLLA internal fixation for fracture treatment may further improve bone formation, which is associated with the increased expression of Runx2 and the enhancement of canonical Wnt signaling.

Effect of low-dose X-ray irradiation and Ti particles on the osseointegration of prosthetic.

Low-dose irradiation (LDI) exhibits a positive effect on osteoblasts and inhibitory effect of inflammation. Here, we test the hypothesis that LDI can promote osseointegration and inhibit the inflammatory membrane formation in the presence of titanium (Ti) particles. Endotoxin-free titanium particles were injected into rabbit, prior to the insertion of a Ti6-Al-4-V sticks pre-coated with hydroxyapatite. Two days after operation, both distal femurs of the animal were exposed to 0.5 Gy X-ray irradiation. All ani-mals were euthanized 8 weeks after the operation. The PINP concentration was determined at day 0, 2, 4, and 8 weeks after operation. Trabecular morphology around the implants 8 weeks after operation was assessed using micro-CT, then the maximum push out force of simples was assessed using biomechanics test. Five samples in each group were chosen for bone histomorphology study without decalcification 8 weeks after operation. The results confirmed that the LDI can significantly improve ingrowth of bone into the prosthetic interface and stability of the prosthesis when there was no wear particles. Although promotion effects for bone formation induced by LDI can be counteracted by wear particles, LDI can significantly inhibit the interface membrane formation around the implant induced by wear particles. Based on these results, we conclude that LDI may be useful for enhancing the stability of prosthesis when there are no wear particles and for inhibiting the interface membrane formation during the early stage of aseptic loosening in the presence of wear particles. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1688-1696, 2016.