FTH1 protects against osteoarthritis by MAPK pathway inhibition of extracellular matrix degradation.

OBJECTIVE: Ferritin heavy chain 1 (FTH1) is an important subunit of ferro-storing proteins and is indispensable for iron metabolism. Though it has been extensively studied in numerous organs and diseases, the relationship between FTH1 and osteoarthritis (OA) is unclear. DESIGN: Primary murine chondrocytes and cartilage explants were treated with FTH1 siRNA for 72 h. Mice were injected with adenovirus expressing FTH1 after destabilized medial meniscus (DMM) surgery. These approaches were used to determine the effect of FTH1 expression on the pathophysiology of OA. RESULTS: FTH1 expression was down regulated in OA patients and mice after DMM surgery. Knock down of FTH1 induced articular cartilage damage and extracellular matrix degradation in cartilage explants. Further, over expression of FTH1 reduced the susceptibility of chondrocytes to ferroptosis and reversed decrements in SOX9 and aggrecan after DMM surgery. Moreover, FTH1 relieved OA by inhibition of the chondrocyte MAPK pathway. CONCLUSION: This study found FTH1 to play an essential role in extracellular matrix degradation, ferroptosis, and chondrocytes senescence during OA progression. Further, injection of adenovirus expressing FTH1 may be a potential strategy for OA prevention and therapy.

Eukaryotic initiation factor 3b regulates the development and progression of breast cancer.

The tumorigenesis of breast cancer is a complex process involving multiple factors, among which abnormal gene expression is a key event. Nevertheless, studies on the regulation of gene expression have focused primarily on the transcriptional level, although the abnormal translation regulation is also closely related to tumorigenesis. Accumulating evidence has indicated the dysregulation of eukaryotic initiation factor (eIF) subunits in a variety of tumors, which contributes to the malignant transformation, tumor growth, metastasis, and the prognosis of patients. In this study, we examined the expression of eIF3b and found an upregulation of eIF3b in breast cancer cell lines as well as tumor tissues. In addition, the expression of eIF3b was related to the tumor stage with highest eIF3b expression in TNM stage III-IV and/or lymph node metastatic breast cancer. Furthermore, in vitro experiments demonstrated that eIF3b knockdown markedly inhibited tumor hyperplasia as well as the migration and invasion of breast cancer cells, while eIF3b overexpression showed the opposite effects. Importantly, eIF3b silencing inhibited the growth and pulmonary metastasis of xenograft tumor in breast cancer mouse model. Mechanistically, we found that eIF3b downregulation suppressed the malignant development of breast cancer by modulating Wnt/ß-catenin pathway. Collectively, our data suggested that eIF3b might not only participate in the tumorigenesis of breast cancer, but also promote the proliferation, invasion, and metastasis of tumor cells. Thus, eIF3b may service as a potential therapeutic target for the treatment of patients with breast cancer.

Rotational osteotomy with single incision and elastic fixation for congenital radioulnar synostosis in children: a retrospective cohort study.

Background: Derotational osteotomy remains the most commonly performed procedure in patients with congenital radioulnar synostosis (CRUS). Bone fixation is mostly performed using K-wires or plates. Many scars, loss of correction and neurovascular complications in the form were the most common complications across the studies. This report introduces a novel, minimally-invasive surgical approach, and reviews our experience. Methods: Twenty-seven children with CRUS were treated using the new technique, including bilateral forearms in 12 cases and unilateral forearm in 15 cases. A transverse osteotomy was performed at the ulnar and radial fusion site, the forearm was derotated osteotomy to the target position, intramedullary nailing was performed, and the elbow was flexed 90 degrees with a long-arm cast after surgery. One week after surgery, the forearm swelling disappeared, the long-arm cast was replaced, the elbow flexed at 90 degrees, and the forearm fixed in the maximum supination position for 4 weeks. Pre- and post-operative positions of the forearm were recorded; the pre- and post-operative activities of daily living (ADL) item scores were recorded for each patient. Results: All patients were followed up postoperatively for a mean duration of 20.7 months. The mean initial pronation deformity was 59.7±12.20 (40 to 100) degrees. The mean correction achieved was 51.2±14.50 degrees, resulting in a mean final position of 8.59±8.10 degrees of supination. The fixed angles of forearm pronation after surgery were corrected to 0-20°, with a mean of 8.33º [standard deviation (SD) 7.98°), and the difference was statistically significant compared with that before surgery (P<0.01). The patients' pre- and post-operative ADL item scores were 3.6 and 4.5, respectively, which was a 0.9-point change and was statistically significant (P<0.01). After surgery, 26 patients obtained good healing, and only one patient had delayed union, which was healed with forearm immobilization for a further month. Conclusions: Rotational osteotomy with single incision and elastic fixation for CRUS in children is a simple operation, and provides advantages including small trauma, fewer postoperative complications, and good efficacy.