Objective. To investigate the capacity of ADAM15, a disintegrin metalloproteinase that is up-regulated in osteoarthritic (OA) cartilage, to protect chondrocytes against apoptosis induced by growth factor deprivation and genotoxic stress.Methods. Caspase 3/7 activity was determined in primary OA and ADAM15-transfected T/C28a4 chondrocytes upon exposure to the DNA-damaging agent camptothecin or serum withdrawal. Camptothecininduced cytotoxicity was determined by measuring cellular ATP content. (Anti-)apoptotic proteins were analyzed by immunoblotting, and levels of messenger RNA (mRNA) for X-linked inhibitor of apoptosis (XIAP) were determined using real-time polymerase chain reaction. RNA interference was applied for down-regulation of ADAM15 and XIAP expression. Immunohistochemistry analysis of normal and OA cartilage samples was performed using XIAP-and ADAM15-specific antibodies.Results. ADAM15-transfected chondrocytes cultured on a collagen matrix displayed significantly reduced caspase 3/7 activity upon serum or intermittent matrix withdrawal, compared with vector-transfected control cells. Apoptosis induction by camptothecin exposure also led to significantly elevated caspase 3/7 activity and reduced cell viability of the vectortransfected compared with ADAM15-transfected chondrocytes. Increased levels of activated caspase 3 and cleaved poly(ADP-ribose) polymerase were detected in the vector controls. XIAP, an inhibitor of activated caspase 3, was significantly up-regulated (ϳ3-fold) at the protein and mRNA levels in ADAM15-transfected chondrocytes upon camptothecin treatment. Specific down-regulation of either ADAM15 or XIAP in OA chondrocytes led to significant sensitization to camptothecininduced caspase 3/7 activity. Immunohistochemical analysis revealed low to moderate XIAP expression in normal specimens and markedly increased XIAP staining, colocalizing with ADAM15, in OA cartilage.Conclusion. ADAM15 conveys antiapoptotic properties to OA chondrocytes that might sustain their potential to better resist the influence of death-inducing stimuli under pathophysiologic conditions.
After introduction of ceramics in total hip replacement, there have been several studies on wear and fracture of the femoral head component. Though reports on fractures are few, we saw four fractures within 2 months. In all patients, a cementless hip prosthesis by four different surgeons was implanted between 3/2001 and 2/2004. In three patients, a ceramic-on-polyethylene pair and in one, a ceramic-on-ceramic pair was used. Only one patient suffered an adequate trauma. The mean survival of the ceramic head was 27 months (11-42). In two patients with polyethylene inlays, the inlay showed signs of wear out due to the fractured head. All four revision surgeries had a good outcome with satisfying results and no complications. Though we observe the postoperative development after implantation of ceramic components closely, we still believe that ceramics in total hip replacement in young and active patients are indicated with good long term results.
Since 1970 we performed 18 operations in hemophilic patients: 7 synovectomies, 2 elongations of the achilles-tendon, 1 hip arthrodesis, 2 endoprosthetic replacements of the hip, 2 intertrochanteric flexion- and varus-osteotomies, 1 excision of a pseudo-tumor and 2 removals of hematomas of the knee joint. The synovectomies were done only in joints affected by frequent hemorrhages. The bleeding frequency could be reduced considerably and the range of motion could be improved. The indication for several other orthopaedic procedures depended on the orthopaedic symptoms. The results were satisfactory without major complications during the healing period. During surgery and the following postoperative care the antihemophilic factor was substituted up to levels between 60 and 120%. The factor VIII or IX was controlled daily and Hb, GOT, GPT and the Australia antigen-antibody on a weekly base. The length of the substitution regimen was dependent on the individual wound healing and the postoperative treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.