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Abstract. the natural product gambogic acid (gA) has been demonstrated to be a promising chemotherapeutic drug for some cancers because of its ability to induce apoptosis and cell cycle arrest. Until now, no studies have looked at the role of gA in osteosarcoma. In this study, we observed the effects of gA on the growth and apoptosis of osteosarcoma cells in vitro. We found that gA treatment inhibits the proliferation of osteosarcoma cells by inducing cell cycle arrest. Moreover, we found that gA induces apoptosis in Mg63, Hos and U2os cells. Furthermore, we showed that gA treatment elevates the Bax/Bcl-2 ratio. gA mediated the g0/g1 phase arrest in U2os cells; this arrest was associated with a decrease in phospho-gsK3-ß (ser9) and the expression of cyclin D1. similarly, in Mg63 cells, gA mediated g2/M cell cycle arrest, which was associated with a decrease in phospho-cdc2 (Thr 161) and cdc25B. Overall, our findings suggest that gA may be an effective anti-osteosarcoma drug because of its capability to inhibit proliferation and induce apoptosis of osteosarcoma cells.

Background High mobility group box 1 (HMGB1) is increased in osteoarthritis (OA) tissue and chondrocytes stimulated with interleukin-1β (IL-1β). Suppression of HMGB1 expression is correlated with reduced inflammatory responses induced by IL-1β. This study aimed to investigate how inhibition of HMGB1 by glycyrrhizin might affect inflammatory responses and viability of OA patient–derived chondrocytes treated with IL-1β. Design The amounts of HMGB1 in the cartilage tissue and synovial fluid in patients with OA were assessed by Western blot and enzyme-linked immunosorbent assay (ELISA). Chondrocytes were extracted from OA patients and maintained in culture. The impact of glycyrrhizin on IL-1β-induced cell toxicity and inflammatory mediators and cytokines, including prostaglandin E2 (PGE2), nitric oxide (NO), proinflammatory cytokines, and metalloproteases (MMPs), were assessed by ELISA, Western blot, quantitative real-time polymerase chain reaction, and the Griess reagent assay. Results We confirmed that HMGB1 was significantly upregulated in specimens acquired from patients with OA. HMGB1 inhibition by glycyrrhizin improved cell viability of chondrocytes treated with IL-1β. Glycyrrhizin suppressed IL-1β-induced upregulation of HMGB1 and inflammatory mediators and cytokines, including PGE2, NO, proinflammatory cytokines, and MMPs. Conclusion Our results indicate that glycyrrhizin may be a potential therapy for OA patients and these promising findings warrant further study for clinical application.

The results in the present study indicate the four important reprogramming proteins, cMyc, Klf4, Oct4, and Sox2, can be produced in soluble format in bacteria with low cost. Our new method thus might be expected to greatly contribute to the future study of iPSCs.

This study evaluated the osteogenic properties of biphasic calcium phosphate (BCP) scaffolds coated with extracellular matrix (ECM) derived in vitro from allogeneic mesenchymal stem cells (MSCs). BCP/ECM and plain BCP scaffolds were seeded with MSCs from F344 rats and cultured in osteoinductive medium. At 1, 7, 14 and 21 days post-seeding, assessments were made of cellularity, alkaline phosphatase (ALP) activity and RNA expression of osteocalcin, bone sialoprotein and osteopontin. MSCs seeded on BCP/ECM scaffolds exhibited significantly higher cellularity, ALP activity and transcript levels for the three genes examined. For the in vivo study, BCP/ECM and BCP scaffolds with and without MSCs were implanted subcutaneously into F344 rats. After four weeks of implantation, the extent of new bone formation and tissue response were examined by histology and histomorphometry; histological evidence showed that the seeded cell scaffolds induced new bone formation at the ectopic site and a higher average ratio of bone in the cell-seeded BCP/ECM scaffold group. Results suggest that modification of the BCP scaffold with an in vitro generated allogeneic ECM can effectively enhance osteogenic properties in vitro and in vivo.