This study explored the role of fibulin-4 in osteosarcoma progression and the possible signaling pathway involved. Fibulin-4 mRNA and protein expression in normal tissue, benign fibrous dysplasia, osteosarcoma, osteosarcoma cell lines, the normal osteoblastic cell line hFOB, and different invasive subclones were evaluated by immunohistochemistry (IHC) or immunocytochemistry (ICC) and real-time reverse transcriptase-polymerase chain reaction (real-time qRT-PCR). Using in vitro functional assays, we analyzed the invasive and proliferative abilities of different osteosarcoma cell lines and subclones with differing invasive potential. To assess the role of fibulin-4 in the invasion and metastasis of osteosarcoma cells, lentiviral vectors with fibulin-4 small hairpin RNA (shRNA) and pLVX-fibulin-4 were constructed and used to infect the highly invasive and low invasive subclones and osteosarcoma cell lines. The effects of fibulin-4 knockdown and upregulation on the biological behavior of osteosarcoma cells were investigated by functional in vitro and in vivo assays. The results revealed that fibulin-4 expression was upregulated in osteosarcoma, and was positively correlated with low differentiation, lymph node metastasis, and poor prognosis. Fibulin-4 was also found to be over-expressed in highly invasive cell lines and in the highly invasive subclones. Fibulin-4 could promote osteosarcoma cell invasion and metastasis by inducing EMT via the PI3K/AKT/mTOR pathway. Collectively, our findings demonstrate that fibulin-4 is a promoter of osteosarcoma development and progression, and suggest a novel therapeutic target for future studies.

This study explored the role of fibulin-3 in osteosarcoma progression and the possible signaling pathway involved. Fibulin-3 mRNA and protein expression in normal tissue, benign fibrous dysplasia, osteosarcoma, osteosarcoma cell lines (HOS and U-2OS), the normal osteoblastic cell line hFOB, and different invasive subclones was evaluated by immunohistochemistry (IHC) or immunocytochemistry (ICC) and real time reverse transcriptase-polymerase chain reaction (real time qRT-PCR). To assess the role of fibulin-3 in the invasion and metastasis of osteosarcoma cells, lentiviral vectors with fibulin-3 small hairpin RNA (shRNA) and pLVX-fibulin-3 were constructed and used to infect the highly invasive and low invasive subclones. The effects of fibulin-3 knockdown and upregulation on the biological behavior of osteosarcoma cells were investigated by functional in vitro and in vivo assays. The results revealed that fibulin-3 expression was upregulated in osteosarcoma, and was positively correlated with low differentiation, lymph node metastasis, and poor prognosis. Fibulin-3 could promote osteosarcoma cell invasion and metastasis by inducing EMT and activating the Wnt/β-catenin signaling pathway. Collectively, our findings demonstrate that fibulin-3 is a promoter of osteosarcoma development and progression, and suggest a novel therapeutic target for future studies.

This meta-analysis indicates that the parameters of outcomes and functional recovery of patients performed with anterior surgery achieve better JOA scores and recovery rates to those with posterior surgery. Though the incidence of complications of anterior surgery are higher than posterior surgery, the anterior directly decompression is advised when the complications could be controlled by advanced surgical technique.

Ferroptosis has recently been discovered as an iron-dependent and non-apoptotic regulated mechanism of cell death. The induction of ferroptosis in tumor cells improves tumor treatment, making it a current research hotspot. Mechanistically, it starts by lipid peroxidation, iron accumulation, reactive oxygen species (ROS) production, and glutathione deprivation, highlighting novel treatment opportunities for many tumors and neurodegenerative disorders. Several tumor cell lines are resistant to ferroptosis inducers, even when the ferroptosis key enzyme glutathione peroxidase 4 (GPX4) is blocked, indicating that other important elements are also involved in this process. Ferroptosis-suppressor-protein 1 (FSP1) was discovered to be one of these elements in addition to a few others such as ferroptotic gatekeepers like GTP cyclohydrolase 1 (GCH1) and dihydroorotate dehydrogenase (DHODH). Osteosarcoma is the most common primary malignant bone tumor observed most frequently in children and adolescents. Several studies demonstrated that ferroptosis plays a critical role in the treatment of osteosarcoma, in particular drug-resistant osteosarcoma cells. We outlined four primary regulators involved in ferroptosis in this article, reviewed previously published studies of ferroptosis in osteosarcoma to provide covert insights about osteosarcoma treatment, and highlighted several critical issues to point out future research possibilities.

Escin, a natural triterpene saponin mixture obtained from the horse chestnut tree ( Aesculus hippocastanum ), has been used for the treatment of chronic venous insufficiency (CVI), hemorrhoids, and edema. However, it is unclear how escin protects against endothelial barrier dysfunction induced by pro‐inflammatory high mobility group protein 1 (HMGB1). Here, we report that escin can suppress (a) HMGB1‐induced overexpression of the aquaporin‐1 (AQP1) water channel in endothelial cells and (b) HMGB1‐induced increases in endothelial cell permeability. This is the first report that escin inhibits AQP1 and alleviates barrier dysfunction in HMGB1‐induced inflammatory response.