Survival protein anoctamin‐6 controls multiple platelet responses including phospholipid scrambling, swelling, and protein cleavage

Scott syndrome is a rare bleeding disorder, characterized by altered Ca2+-dependent platelet signaling with defective phosphatidylserine (PS) exposure and microparticle formation, and is linked to mutations in the ANO6 gene, encoding anoctamin (Ano) 6. We investigated how the complex platelet phenotype of this syndrome is linked to defective expression of Anos or other ion channels. Mice were generated with heterozygous of homozygous deficiency in Ano6, Ano1, or Ca2+-dependent K(Ca)3.1Gardos channel. Platelets from these mice were extensively analyzed on molecular functions and compared with platelets from a patient with Scott syndrome. Deficiency in Ano1 or Gardos channel did not reduce platelet responses compared with control mice (P > 0.1). In 2 mouse strains, deficiency in Ano6 resulted in reduced viability with increased bleeding time to 28.6min (control 6.4min, P 0.05) with reduced PS exposure (265 to 90%); 2) lowered Ca2+-dependent swelling (280%) and membrane blebbing (-90%); 3) reduced calpain-dependent protein cleavage (-60%); and 4) moderately affected apoptosis-dependent PS exposure. In conclusion, mouse deficiency of Ano6 but not of other channels affects viability and phenocopies the complex changes in platelets from hemostatically impaired patients with Scott syndrome

Giant cell tumour of bone: morphological, biological and histogenetical aspects

The giant cell tumour of bone (GCT) is a locally aggressive intraosseous neoplasm of obscure biological behaviour. Although well defined in clinical, radiological and histological terms, detailed information on its biological development is still relatively incomplete. The tumoral tissue consists of three cell types – the neoplastic giant cell tumour stromal cells (GCTSC), representing the proliferative fraction, secondarily recruited mononuclear histiocytic cells (MNHC) and multinuclear giant cells (MNGC). These cellular components interact together with factors that have a role in regulating osteoclast function in normal bone tissue (e.g. RANK, RANKL, OPG, M-CSF). Recent publications suggest that the neoplastic stromal cells express differentiation features of mesenchymal stem cells. Further research of the pathogenesis of GCT as well as the complex interactions of its cellular populations may provide the knowledge necessary for developing approaches for a biological-based therapy of this neoplasm