Cytokine-induced osteoprotegerin expression protects pancreatic beta cells through p38 mitogen-activated protein kinase signalling against cell death.

AIMS/HYPOTHESIS: Pro-inflammatory cytokines play a crucial role in immune-mediated beta cell destruction, an essential mechanism in the pathogenesis of type 1 diabetes mellitus. Microarray analysis recently identified osteoprotegerin (OPG; now known as tumour necrosis factor receptor superfamily, member 11b [TNFRSF11B]) as a cytokine-induced gene in beta cells. The aim of the present study was to characterise the functional role and signalling pathways of OPG that are involved in cytokine-induced beta cell death. MATERIALS AND METHODS: As cellular models, the rat beta cell line INS-1E and human primary pancreatic islets were employed. The effects of IL-1beta and TNF-alpha on OPG expression were characterised by northern blot and immunoassay. The effect of OPG on beta cell survival was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Signalling pathways were evaluated by western blot analysis using antibodies against p38 mitogen-activated protein kinases (MAPK), c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2. RESULTS: The INS-1E cell line and primary pancreatic islets expressed OPG mRNA and secreted OPG protein, both of which were enhanced by IL-1beta and TNF-alpha. Exposure to IL-1beta resulted in sustained phosphorylation of p38 MAPK in INS-1E cells and subsequent cell death. Administration of exogenous OPG prevented both IL-1beta-induced beta cell death and sustained p38 MAPK phosphorylation. CONCLUSIONS/INTERPRETATION: Our data indicate that cytokine-induced production of OPG may protect beta cells from further damage. This protective effect is, at least in part, mediated through inhibition of p38 MAPK phosphorylation. Thus OPG is an autocrine or paracrine survival factor for beta cells.

[The hip head-conserving management of traumatic medial cervical hip fractures with big-fragment screws: a biomechanical examination]. / Die kopferhaltende operative Versorgung der traumatischen medialen Schenkelhalsfraktur mit Grossfragmentschrauben -- eine biomechanische Prüfung.

AIM: With the growing number of elderly people in the population and the increasing incidence of proximal hip fractures the question of how to manage the medial hip head fracture is of increasing importance. Especially in Hungary and the Scandinavian countries surgeons prefer hip head-conserving therapy although the redislocation of this fracture and necrosis of the hip head opposes this point of view. METHOD: Encouraged by two theoretical and mathematical calculations, we tested two different possibilities to screw hip head fractures. RESULTS: Our results show that the hip head-conserving therapy with two cranial screws and a three-point-supported screw at Adam's arc has essential biomechanical advantages compared with the situation after conventional osteosynthesis. CONCLUSION: This result encourages us to prefer the minimally invasive head-conserving therapy of medial hip head fractures, especially for treatment of Pauwell's I and II injuries.