Trojan-like internalization of anatase titanium dioxide nanoparticles by human osteoblast cells

Dentistry and orthopedics are undergoing a revolution in order to provide more reliable, comfortable and long-lasting implants to patients. Titanium (Ti) and titanium alloys have been used in dental implants and total hip arthroplasty due to their excellent biocompatibility. However, Ti-based implants in human body suffer surface degradation (corrosion and wear) resulting in the release of metallic ions and solid wear debris (mainly titanium dioxide) leading to peri-implant inflammatory reactions. Unfortunately, our current understanding of the biological interactions with titanium dioxide nanoparticles is still very limited. Taking this into consideration, this study focuses on the internalization of titanium dioxide nanoparticles on primary bone cells, exploring the events occurring at the nano-bio interface. For the first time, we report the selective binding of calcium (Ca), phosphorous (P) and proteins from cell culture medium to anatase nanoparticles that are extremely important for nanoparticle internalization and bone cells survival. In the intricate biological environment, anatase nanoparticles form bio-complexes (mixture of proteins and ions) which act as a kind of ‘Trojan-horse’ internalization by cells. Furthermore, anatase nanoparticles-induced modifications on cell behavior (viability and internalization) could be understand in detail. The results presented in this report can inspire new strategies for the use of titanium dioxide nanoparticles in several regeneration therapies

Long-term culture of cholangiocytes from liver fibro-granulomatous lesions

BACKGROUND: Extensive bile duct proliferation is a key feature of the tissue reaction to clinical and experimental forms of liver injury. Experimental infection of mice by Schistosoma mansoni is a well-studied model of liver fibrosis with bile duct hyperplasia. However, the regulatory mechanisms of bile duct changes are not well understood. In this study we report the reproducible isolation of long-term cultures of cholangiocytes from mice livers with schistosomal fibrosis. METHODS: We have isolated a cholangiocyte cell line from Schistosoma-induced liver granulomas using a combination of methods including selective adhesion and isopyknic centrifugation in Percoll. RESULTS: The cell line was characterized by morphological criteria in optical and transmission electron microscopy, ability to form well differentiated ductular structures in collagen gels and by a positive staining for cytokeratin 18 and cytokeratin 19. To our knowledge, this is the first murine cholangiocyte cell line isolated from schistosomal fibrosis reported in the literature. CONCLUSION: After 9 months and 16 passages this diploid cell line maintained differentiated characteristics and a high proliferative capacity. We believe the method described here may be a valuable tool to study bile duct changes during hepatic injury

TGF β1 and PDGF AA override Collagen type I inhibition of proliferation in human liver connective tissue cells

BACKGROUND: A marked expansion of the connective tissue population and an abnormal deposition of extracellular matrix proteins are hallmarks of chronic and acute injuries to liver tissue. Liver connective tissue cells, also called stellate cells, derived from fibrotic liver have been thoroughly characterized and correspond phenotypically to myofibroblasts. They are thought to derive from fat-storing Ito cells in the perisinusoidal space and acquire a contractile phenotype when activated by tissue injury. In the last few years it has become evident that several peptide growth factors such as PDGF AA and TGF-β are involved in the development of fibrosis by modulating myofibroblast proliferation and collagen secretion. The fact that during the development of chronic fibrosis there is concomitant deposition of collagen, a known inhibitory factor, and sustained cell proliferation, raises the possibility that stellate cells from chronic liver fibrosis patients fail to respond to normal physiologic controls. METHODS: In this study we address whether cells from fibrotic liver patients respond to normal controls of proliferation. We compared cell proliferation of primary human liver connective tissue cells (LCTC) from patients with liver fibrosis and skin fibroblasts (SF) in the presence of collagens type I and IV; TGF-β, PDGF AA and combinations of collagen type I and TGF-β or PDGF AA. RESULTS: Our results indicate that despite displaying normal contact and collagen-induced inhibition of proliferation LCTC respond more vigorously to lower concentrations of PDGF AA. In addition, we show that collagen type I synergizes with growth factors to promote mitogenesis of LCTC but not SF. CONCLUSIONS: The synergistic interaction of growth factors and extracellular matrix proteins may underlie the development of chronic liver fibrosis

The bone marrow compartment is modified in the absence of galectin-3

Galectin-3 (gal-3) is a β-galactoside binding protein present in multivalent complexes with an extracellular matrix and with cell surface glycoconjugates. In this context, it can deliver a variety of intracellular signals to modulate cell activation, differentiation and survival. In the hematopoietic system, it was demonstrated that gal-3 is expressed in myeloid cells and surrounding stromal cells. Furthermore, exogenous and surface gal-3 drive the proliferation of myeloblasts in a granulocyte–macrophage colony-stimulating factor (GM-CSF)-dependent manner. Here, we investigated whether gal-3 regulates the formation of myeloid bone marrow compartments by studying galectin-3−/− mice (gal-3−/−) in the C57BL/6 background. The bone marrow histology of gal-3−/− mice was significantly modified and the myeloid compartments drastically disturbed, in comparison with wild-type (WT) animals. In the absence of gal-3, we found reduced cell density and diaphyseal disorders containing increased trabecular projections into the marrow cavity. Moreover, myeloid cells presented limited capacity to differentiate into mature myeloid cell populations in gal-3−/− mice and the number of hematopoietic multipotent progenitors was increased relative to WT animals. In addition, bone marrow stromal cells of these mice had reduced levels of GM-CSF gene expression. Taken together, our data suggest that gal-3 interferes with hematopoiesis, controlling both precursors and stromal cells and favors terminal differentiation of myeloid progenitors rather than proliferation

Global Diversity of Sponges (Porifera)

With the completion of a single unified classification, the Systema Porifera (SP) and subsequent development of an online species database, the World Porifera Database (WPD), we are now equipped to provide a first comprehensive picture of the global biodiversity of the Porifera. An introductory overview of the four classes of the Porifera is followed by a description of the structure of our main source of data for this paper, the WPD. From this we extracted numbers of all ‘known’ sponges to date: the number of valid Recent sponges is established at 8,553, with the vast majority, 83%, belonging to the class Demospongiae. We also mapped for the first time the species richness of a comprehensive set of marine ecoregions of the world, data also extracted from the WPD. Perhaps not surprisingly, these distributions appear to show a strong bias towards collection and taxonomy efforts. Only when species richness is accumulated into large marine realms does a pattern emerge that is also recognized in many other marine animal groups: high numbers in tropical regions, lesser numbers in the colder parts of the world oceans. Preliminary similarity analysis of a matrix of species and marine ecoregions extracted from the WPD failed to yield a consistent hierarchical pattern of ecoregions into marine provinces. Global sponge diversity information is mostly generated in regional projects and resources: results obtained demonstrate that regional approaches to analytical biogeography are at present more likely to achieve insights into the biogeographic history of sponges than a global perspective, which appears currently too ambitious. We also review information on invasive sponges that might well have some influence on distribution patterns of the future