Periprosthetic osteolysis-bone loss in the vicinity of a prosthesis-is the most serious problem limiting the longevity of artificial joints. It is caused by bone-resorptive responses to wear particles originating from the articulating surface. This study investigated the effects of graft polymerization of our original biocompatible phospholipid polymer 2-methacryloyloxyethyl phosphorylcholine (MPC) onto the polyethylene surface. Mechanical studies using a hip-joint simulator revealed that the MPC grafting markedly decreased the friction and the amount of wear. Osteoclastic bone resorption induced by subperiosteal injection of particles onto mouse calvariae was abolished by the MPC grafting on particles. MPC-grafted particles were shown to be biologically inert by culture systems with respect to phagocytosis and resorptive cytokine secretion by macrophages, subsequent expression of receptor activator of NF-kappaB ligand in osteoblasts, and osteoclastogenesis from bone marrow cells. From the mechanical and biological advantages, we believe that our approach will make a major improvement in artificial joints by preventing periprosthetic osteolysis.

Osteoarthritis (MIM 165720), characterized by degeneration of articular cartilage, is the most common form of human arthritis and a major concern for aging societies worldwide. Epidemiological and genetic studies have shown that osteoarthritis is a polygenic disease. Here, we report that the gene encoding growth differentiation factor 5 (GDF5) is associated with osteoarthritis in Asian populations. A SNP in the 5' UTR of GDF5 (+104T/C; rs143383) showed significant association (P = 1.8 x 10(-13)) with hip osteoarthritis in two independent Japanese populations. This association was replicated for knee osteoarthritis in Japanese (P = 0.0021) and Han Chinese (P = 0.00028) populations. This SNP, located in the GDF5 core promoter, exerts allelic differences on transcriptional activity in chondrogenic cells, with the susceptibility allele showing reduced activity. Our findings implicate GDF5 as a susceptibility gene for osteoarthritis and suggest that decreased GDF5 expression is involved in the pathogenesis of osteoarthritis.

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