Two types of bone necrosis in the middle triassic pistosaurus longaevus bones: The results of integrated studies

Avascular necrosis, diagnosed on the basis of either a specific pathological modification of the articular surfaces of bone or its radiologic appearance in vertebral centra, has been recognized in many Mesozoic marine reptiles as well as in present-day marine mammals. Its presence in the zoological and paleontologic record is usually associated with decompression syndrome, a disease that affects secondarily aquatic vertebrates that could dive. Bone necrosis can also be caused by infectious processes, but it differs in appearance from decompression syndrome-associated aseptic necrosis. Herein, we report evidence of septic necrosis in the proximal articular surface of the femur of a marine reptile, Pistosaurus longaevus, from the Middle Triassic of Poland and Germany. This is the oldest recognition of septic necrosis associated with septic arthritis in the fossil record so far, and the mineralogical composition of pathologically altered bone is described herein in detail. The occurrence of septic necrosis is contrasted with decompression syndrome-associated avascular necrosis, also described in Pistosaurus longaevus bone from Middle Triassic of Germany

Control of Cell Migration and Inflammatory Mediators Production by CORM-2 in Osteoarthritic Synoviocytes

BackgroundOsteoarthritis (OA) is the most widespread degenerative joint disease. Inflamed synovial cells contribute to the release of inflammatory and catabolic mediators during OA leading to destruction of articular tissues. We have shown previously that CO-releasing molecules exert anti-inflammatory effects in animal models and OA chondrocytes. We have studied the ability of CORM-2 to modify the migration of human OA synoviocytes and the production of chemokines and other mediators sustaining inflammatory and catabolic processes in the OA joint.Methodology/Principal FindingsOA synoviocytes were stimulated with interleukin(IL)-1β in the absence or presence of CORM-2. Migration assay was performed using transwell chambers. Gene expression was analyzed by quantitative PCR and protein expression by Western Blot and ELISA. CORM-2 reduced the proliferation and migration of OA synoviocytes, the expression of IL-8, CCL2, CCL20, matrix metalloproteinase(MMP)-1 and MMP-3, and the production of oxidative stress. We found that CORM-2 reduced the phosphorylation of extracellular signal-regulated kinase1/2, c-Jun N-terminal kinase1/2 and to a lesser extent p38. Our results also showed that CORM-2 significantly decreased the activation of nuclear factor-κB and activator protein-1 regulating the transcription of chemokines and MMPs in OA synoviocytes.Conclusion/SignificanceA number of synoviocyte functions relevant in OA synovitis and articular degradation can be down-regulated by CORM-2. These results support the interest of this class of agents for the development of novel therapeutic strategies in inflammatory and degenerative conditions

Peroxynitrite mediates calcium-dependent mitochondrial dysfunction and cell death via activation of calpains

10.1096/fj.03-1096fjeFASEB Journal18121395-1397FAJO

S100A8/S100A9 and their association with cartilage and bone

S100A8 and S100A9 are calcium-binding proteins expressed in myeloid cells and are markers of numerous inflammatory diseases in humans. S100A9 has been associated with dystrophic calcification in human atherosclerosis. Here we demonstrate S100A8 and S100A9 expression in murine and human bone and cartilage cells. Only S100A8 was seen in preosteogenic cells whereas osteoblasts had variable, but generally weak expression of both proteins. In keeping with their reported high-mRNA expression, S100A8 and S100A9 were prominent in osteoclasts. S100A8 was expressed in alkaline phosphatase-positive hypertrophic chondrocytes, but not in proliferating chondrocytes within the growth plate where the cartilaginous matrix was calcifying. S100A9 was only evident in the invading vascular osteogenic tissue penetrating the degenerating chondrocytic zone adjacent to the primary spongiosa, where S100A8 was also expressed. Whilst, S100A8 has been shown to be associated with osteoblast differentiation, both S100A8 and S100A9 may contribute to calcification of the cartilage matrix and its replacement with trabecular bone, and to regulation of redox in bone resorption.H. Zreiqat, C. R. Howlett, S. Gronthos, D. Hume and C. L. Gecz