Osteoclasts are multinuclear giant cells responsible for bone resorption in lytic bone diseases such as osteoporosis, arthritis, periodontitis, and bone tumors. Due to the severe side-effects caused by the currently available drugs, a continuous search for novel bone-protective therapies is essential. Artesunate (Art), the water-soluble derivative of artemisinin has been investigated owing to its anti-malarial properties. However, its effects in osteoclastogenesishave not yet been reported. In this study, Art was shown to inhibit the nuclear factor-κB ligand

Background/Aims: Extensive osteoclast formation plays a critical role in bone diseases, including rheumatoid arthritis, periodontitis and the aseptic loosening of orthopedic implants. Thus, identification of agents that can suppress osteoclast formation and bone resorption is important for the treatment of these diseases. Monocrotaline (Mon), the major bioactive component of crotalaria sessiliflora has been investigated for its anti-cancer activities. However, the effect of Mon on osteoclast formation and osteolysis is not known. Methods: The bone marrow macrophages (BMMs) were cultured with M-CSF and RANKL followed by Mon treatment. Then the effects of Mon on osteoclast differentiation were evaluated by counting TRAP (+) multinucleated cells. Moreover, effects of Mon on hydroxyapatite resorption activity of mature osteoclast were studied through resorption areas measurement. The involved potential signaling pathways were analyzed by performed Western blotting and quantitative real-time PCR examination. Further, we established a mouse calvarial osteolysis model to measure the osteolysis suppressing effect of Mon in vivo. Results: In this study, we show that Mon can inhibit RANKL-induced osteoclast formation and function in a dose-dependent manner. Mon inhibits the expression of osteoclast marker genes such as tartrate-resistant acid phosphatase (TRAP) and cathepsin K. Furthermore, Mon inhibits RANKL-induced the activation of p38 and JNK. Consistent with in vitro results, Mon exhibits protective effects in an in vivo mouse model of LPS-induced calvarial osteolysis. Conclusion: Taken together our data demonstrate that Mon may be a potential prophylactic anti-osteoclastic agent for the treatment of osteolytic diseases caused by excessive osteoclast formation and function.

Accumulating evidence has suggested that gene therapy plays critical roles in glioma treatment. Our previous studies demonstrated that miR-451 could be used as a tumor suppressor via targeting CAB39. But the ability for the targeted delivery of miR-451 to glioma was a significant issue. Bone marrow mesenchymal stem cells (BMSCs) have been used for systemic delivery of therapeutic genes to solid tumors. In the present study, hBMSCs were used as gene therapy non-viral vectors of miR-451 to treat glioma cells in vitro and in vivo. First, following the treatment of glioma cells with the culture medium of miR-451-loaded hBMSCs via lentivirus, overexpression of miR-451 in glioma cells suppressed its proliferation, migration and invasion, but enhanced cell apoptosis by targeting CAB39 and the LKB1/AMPK/HIF-1α/VEGF pathways. Secondly, Transwell migration assays further demonstrated the chemotaxis of BMSCs to glioma conditioned media in vitro. Lastly, it was verified that the miR-451-loaded hBMSCs could effectively deliver miR-451 to the tumor region and prolong the survival in xenograft model assays. These results indicated that gene therapy using hBMSCs as vehicles was highly effective in a mice glioma model and therefore hold considerable prospects of clinical transformation.