Malignant transformation of Slp65-deficient pre-B cells involves disruption of the Arf-Mdm2-p53 tumor suppressor pathway

The adapter protein Slp65 is a key component of the precursor-B (pre-B) cell receptor. Slp65-deficient mice spontaneously develop pre-B cell leukemia, but the mechanism by which Slp65(-/-) pre-B cells become malignant is unknown. Loss of Btk, a Tec-family kinase that cooperates with Slp65 as a tumor suppressor, synergizes with deregulation of the c-Myc oncogene during lymphoma formation. Here, we report that the presence of the immunoglobulin heavy chain transgene V(H)81X prevented tumor development in Btk(-/-)Slp65(-/-) mice. This finding paralleled the reported effect of a human immunoglobulin heavy chain transgene on lymphoma development in E mu-myc mice, expressing transgenic c-Myc. Because activation of c-Myc strongly selects for spontaneous inactivation of the p19(Arf)-Mdm2-p53 tumor suppressor pathway, we investigated whether disruption of this pathway is a common alteration in Slp65(-/-) pre-B cell tumors. We found that combined loss of Slp65 and p53 in mice transformed pre-B cells very efficiently. Aberrations in p19(Arf), Mdm2, or p53 expression were found in all Slp65(-/-)(n = 17) and Btk(-/-)Slp65(-/-)(n = 32) pre-B cell leukemias analyzed. In addition, 9 of 10 p53(-/-)Slp65(-/-) pre-B cell leukemias manifested significant Mdm2 protein expression. These data indicate that malignant transformation of Slp65(-/-) pre-B cells involves disruption of the p19(Arf)-Mdm2-p53 tumor suppressor pathway. (Blood. 2010; 115: 1385-1393

In vitro evaluation of osteoblastic cell adhesion on machined osseointegrated implants

At present the major consideration in planning an implant design is to seek biocompatible surfaces that promote a favorable response from both cells and host tissues. Different treatments of implant surfaces may modulate the adhesion, proliferation and phenotypic expression of osteoblastic cells. For this reason, the aim of the present study was to evaluate the biocompatibility of an implant surface, observing adhesion, cell morphology and proliferation of osteoblast-like cells cultivated on a commercially available titanium dental implant (Titamax Liso®, Neodent, Curitiba, PR, Brazil). The implant samples were immersed into an osteoblast-like cell (Osteo-1) suspension for a period of 24, 48 and 72 hours. After seeding the cells, the samples were prepared for analyses through scanning electron microscopy. Based on the surface analysis, the osteoblastic cells adhered to the machined surface after 24 hours in culture. In 48 hours, the cells spread over the implant surface, and after 72 hours a proliferation of cells with large and flat bodies was observed over the machined implant surface. These results demonstrate that the machined titanium surface studied is biocompatible since it allowed adhesion and proliferation of the osteoblast-like cells, in addition to preserving cell integrity and the morphologic characteristics of cells during the studied period

The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder

A key tenet of bone tissue engineering is the development of scaffold materials that can stimulate stem cell differentiation in the absence of chemical treatment to become osteoblasts without compromising material properties. At present, conventional implant materials fail owing to encapsulation by soft tissue, rather than direct bone bonding. Here, we demonstrate the use of nanoscale disorder to stimulate human mesenchymal stem cells (MSCs) to produce bone mineral in vitro, in the absence of osteogenic supplements. This approach has similar efficiency to that of cells cultured with osteogenic media. In addition, the current studies show that topographically treated MSCs have a distinct differentiation profile compared with those treated with osteogenic media, which has implications for cell therapies.<br/