Arctigenin Suppresses the Proliferation and Metastasis, and Induces Apoptosis and Cycle Arrest of Osteosarcoma Cells by inhibiting HMOX1 Expression.

BACKGROUND: Osteosarcoma is the most common malignant bone tumor, with highly proliferative and metastatic properties. Previous studies have reported that arctigenin (Arc), a bioactive lignin compound, showed excellent anti-tumor activities in a variety of human cancers. However, its role in osteosarcoma has not been studied. OBJECTIVE: We aimed to investigate the anti-tumor effects of Arc on osteosarcoma cell proliferation, migration, invasion, apoptosis, and cell cycle. METHODS: Effects of Arc on osteosarcoma cell proliferation were detected by MTT and colony formation assay. Flow cytometry analysis was performed to assess the cell apoptosis and cycle arrest. Transwell assay was used to evaluate the capability of migration and invasion. qRT-PCR and Western blot were employed to determine the changes in mRNA and protein levels. RESULTS: Arc could significantly suppress the proliferation, colony formation, and induce cell apoptosis and S phase cycle arrest of MG63 and U-2 OS cells in a dose-dependent manner. In addition, we also observed an inhibitory effect of Arc treatment on osteosarcoma cell invasion, migration, and epithelial-mesenchymal transition (EMT). HMOX1, encoding enzyme heme oxygenase-1, was predicted to be a candidate target of Arc using STITCH. Arc treatment significantly reduced the mRNA and protein levels of HMOX1. Furthermore, overexpression of HMOX1 could partly reverse the inhibitory effects of Arc on osteosarcoma cell malignant phenotypes. CONCLUSION: Our results suggest that Arc inhibits the proliferation, metastasis and promotes cell apoptosis and cycle arrest of osteosarcoma cells by downregulating HMOX1 expression.

Alisol A 24-acetate ameliorates osteoarthritis progression by inhibiting reactive oxygen species and inflammatory response through the AMPK/mTOR pathway.

INTRODUCTION: Osteoarthritis is a degenerative knee joint disease featured with articular cartilage degeneration and inflammation. Alisol A 24-acetate (ALA-24A) is an active triterpene that has antioxidant and anti-inflammatory pharmacological properties. However, its effect and molecular mechanism on osteoarthritis progression have not been reported. METHODS: IL-1ß-induced chondrocyte injury model and monosodium iodoacetate (MIA)-induced rat osteoarthritis model were used. The protective effects of ALA-24A on osteoarthritis were evaluated by determining cell viability, extracellular matrix (ECM) degradation, inflammatory response and oxidative stress using CCK-8 assay, Western blot, ELISA, and DCFH-DA fluorescent probe. The severity and matrix degradation of articular cartilage were assessed by histopathological and immunohistochemical examination. RESULTS: We found that ALA-24A attenuated IL-1ß-induced cell viability inhibition Moreover, ALA-24A suppressed expression levels of ECM degradation-related genes ADAMTS5 and MMP13, and promoted expression levels of ECM synthesis-related genes Aggrecan and Collagen II. In addition, ALA-24A treatment decreased reactive oxygen species (ROS) production and increased antioxidant enzymes (SOD, CAT, and GSH-px) activities, while increased MDA levels. The inflammatory levels of NO, PGE2, TNF-α, and IL-6 were also reduced following treatment with ALA-24A. Our data also revealed that ALA-24A treatment triggered p-AMPK upregulation and p-mTOR downregulation. In rat osteoarthritis model, ALA-24A treatment significantly alleviated the severity and matrix degradation of articular cartilage comparted with model group. CONCLUSIONS: Our findings suggested a protective role of ALA-24A against osteoarthritis by inhibiting ROS and inflammatory response. Furthermore, ALA-24A might be a promising therapeutic option for osteoarthritis treatment.

[EFFECTIVENESS OF HIGH TIBIAL OSTEOTOMY ASSISTED BY THREE- DIMENSIONAL PRINTING TECHNOLOGY FOR CORRECTION OF VARUS KNEE WITH OSTEOARTHRITIS].

OBJECTIVE: To evaluate the effectiveness of high tibial osteotomy (HTO) assisted by three-dimensional (3-D) printing technology for correction of varus knee with osteoarthritis. METHODS: Between January 2014 and June 2015, 16 patients (20 knees) with varus knee and osteoarthritis underwent HTO assisted by 3-D printing technology; a locking compression plate was used for internal fixation after HTO. There were 6 males and 10 females, aged 30-60 years (mean, 45.5 years). The disease duration was 1-10 years (mean, 6.2 years). The unilateral knee was involved in 12 cases and bilateral knees in 4 cases. According to Koshino's staging system, 3 knees were classified as stage I, 7 knees as stage II, 8 knees as stage III, and 2 knees as stage IV. Preoperative Hospital for Special Surgery (HSS) knee score was 63.8 ± 2.2; the femorotibial angle was (184.8 ± 2.9)°; and Insall-Salvati index was 1.03 ± 0.13. RESULTS: All the wounds healed primarily, and no complication of infection, osteofacial compartment syndrom, or deep vein thrombosis was observed. All patients were followed up 6-18 months (mean, 12.6 months). Personal paralysis was observed in 1 case (1 knee), and was cured after expectant treatment. Bone union time was 2.7-3.4 months (mean, 2.9 months). At 6 months after operation, the femorotibial angle was (173.8 ± 2.0)°, showing significant difference when compared with preoperative one (t = 11.70, P = 0.00); Insall-Salvati index was 1.04 ± 0.12, showing no significant difference when compared with preoperative one (t = -0.20, P = 0.85); and HSS knee score was significantly increased to 88.9 ± 3.1 (t = -25.44, P = 0.00). At last follow-up, the results were excellent in 13 knees, good in 6 knees, fair in 1 knee, and the excellent and good rate was 95%. CONCLUSION: 3-D printing cutting block can greatly improve the accuracy of HTO, avoid repeated X-ray and multiple osteotomy, shorten the operation time, and ensure better effectiveness for correction of varus knee with osteoarthritis.