Osteopontin-induced brown adipogenesis from white preadipocytes through a PI3K-AKT dependent signaling.

Recent studies have shown that OPN (osteopontin) plays critical roles in cell survival, differentiation, bio-mineralization, cancer and cardiovascular remodeling. However, its roles in the differentiation of brown adipocytes and the underlying mechanisms remain unclear. Therefore, the aim of this study was to investigate the roles of OPN in the brown adipogenesis and the underlying mechanisms. It was shown that the OPN successfully induced the differentiation of 3T3-L1 white preadipocytes into the PRDM16(+) (PRD1-BF1-RIZ1 homologous domain containing 16) and UCP-1(+) (uncoupling protein-1) brown adipocytes in a concentration and time-dependent manner. Also, activation of PI3K (phosphatidylinositol 3-kinase)-AKT pathway was required for the OPN-induced brown adipogenesis. The findings suggest OPN plays an important role in promoting the differentiation of the brown adipocytes and might provide a potential novel therapeutic approach for the treatment of obesity and related disorders.

[Osteogenic and adipogenic differentiation of bone marrow multipotent mesenchymal stem cells in the mice with hemorrhagic anemia].

This study was aimed to investigate the effects of osteogenic and adipogenic differentiation of bone marrow multipotent mesenchymal stem cells (MSC) on hematopoiesis. A hemorrhagic anemia mouse model was established by exsanguinating of 0.3 ml blood from angular vein every 1-2 days for 4 weeks. The number of leukocytes, erythrocytes and neutrophils, hemoglobin level, ratio of reticulocyte in peripheral blood and bone marrow cell colony forming unit (CFU) were detected for the identification of the model. The differential potential of MSC in the hemorrhagic anemia mice were identified by CFU-F, histopathologic analysis, and osteogenesis and adipogenesis-related gene expression. The results showed that the erythrocyte numbers of peripheral blood and hemoglobin level decreased in the hemorrhagic anemia mice compared with the control, while the ratio of reticulocyte, the numbers of bone marrow cells and the CFU increased. Furthermore, the numbers of CFU-F, bone marrow hematopoietic cells, and osteogenic cells increased. However, the number of adipocytes decreased. Expressions of osteogenesis-related genes Runx2 and OSX were up-regulated, and adipogenesis-related genes aP2 and PPARγ2 were down-regulated in the hemorrhagic anemia mice compared with the control. It is concluded that the potential of osteogenic differentiation of MSC is enhanced, while the potential of adipogenic differentiation of MSC is weakened in the hemorrhagic anemia mice.

Hematopoietic recovery following chemotherapy is improved by BADGE-induced inhibition of adipogenesis.

This study was designed to investigate the role of increased adipocytes in the bone marrow (BM) niche induced by high-dose chemotherapy in hematopoietic recovery. Arabinosylcytosine (Ara-C) was administered to adult C57BL/6J mice to induce adipogenesis in the BM. We investigated the effects of adipogenesis on hematopoietic recovery following chemotherapy, using the peroxisome proliferator-activated receptor gamma inhibitor, bisphenol A diglycidyl ether (BADGE). Adipocyte hyperplasia could be induced by Ara-C treatment in BM and inhibited by BADGE. The accelerated recovery of leukocyte counts, increased colony forming units, and a higher proportion of Ki67(+)CD45(+) BM cells and Ki67(+)Lin(-)Sca1(+)c-kit(+) hematopoietic stem cells were observed in the long bone marrow of adipocyte-inhibited mice, as well as an increase in the number of CD45(+) BM cells in the tail fatty marrow compared to controls. Adipocytes participated in creating a distinctive niche for hematopoietic cells. In addition, lower expression of stromal cell-derived factor-1α and hypoxia-inducible factor-1 alpha were detected in the BADGE-treated group. These results indicate that hematopoietic recovery is improved following chemotherapy in adipogenesis-inhibited mice. In addition, adipocytes may create an individual niche that affects the proliferation and migration of hematopoietic cells in vitro and in vivo.

[Induction of apoptosis of leukemic tumor cells in mouse model with G-quadruplex ligand Tel03].

This study was aimed to investigate the anti-leukemia activity of Tel03 in vivo. The K562 xenografted leukemia model was established and mice were divided randomly into three groups. Mice of different group were treated with PBS (control), 5 mg/kg Tel03 or 15 mg/kg Tel03 (ip, twice a week) respectively. Tumor volume, body weight and other behavior were observed regularly. Cell apoptosis was detected with TUNEL assay and the expression levels of Bcl-2 and Bax were detected by Western blot. The results indicated that Tel03 exerted anti-leukemia activity in mouse model. Tel03 significantly reduced tumor volume in Tel03-treated group compared with control. In addition, 5 mg/kg Tel03 induced cell apoptosis without exerting apparent toxicity in mice. After Tel03 treatment, the expression of Bcl-2 was inhibited, however, the expression of Bax was up-regulated. It is concluded that G-quadruplex ligand Tel03 can induce cell apoptosis in leukemia mouse model, and this agent may be a potential anticancer drug.