Search

Background and purpose Osteochondral defects have a limited capacity for repair. We therefore investigated the effects of tumor necrosis factor (TNF) signal blockade by etanercept (human recombinant soluble TNF receptor) on the repair of osteochondral defects in rabbit knees. Material and methods Osteochondral defects (5 mm in diameter) were created in the femoral patellar groove in rabbits. Soon after the procedure, a first subcutaneous injection of etanercept was performed. This single injection or, alternatively, 4 injections in total (twice a week for 2 weeks) were given. Each of these 2 groups was divided further into 3 subgroups: a low-dose group (0.05 μg/kg), an intermediate-dose group (0.4 μ g/kg), and a high-dose group (1.6 μ g /kg) with 19 rabbits in each. As a control, 19 rabbits were injected with water alone. The rabbits in each subgroup were killed 4 weeks (6 rabbits), 8 weeks (6 rabbits), or 24 weeks (7 rabbits) after surgery and repair was assessed histologically. Results Histological examination revealed that the natural process of repair of the osteochondral defects was promoted by 4 subcutaneous injections of intermediate-dose etanercept and by 1 or 4 injections of high-dose etanercept at the various time points examined postoperatively (4, 8, and 24 weeks). Western blot showed that rabbit TNFα had a high affinity for etanercept. Interpretation Blocking of TNF by etanercept enabled repair of osteochondral defects in rabbit knee. Anti-TNF therapy could be a strategy for the use of tissue engineering for bone and cartilage repair. [ABSTRACT FROM AUTHOR]

Background The etiology of osteoarthritis (OA) is multifactorial and current research attributes it to a complex network of biochemical factors. We attempted to identify important molecules in OA joint destruction. Patients and methods Synovium was collected from 2 women with hip OA. Total RNA was extracted from the combined synovium. Messenger RNAs (mRNAs) were randomly sequenced for identification with the oligo-capping method. mRNA expression of 9 genes that were found to be frequently expressed was compared in synovium from 7 OA patients and 2 control patients with no signs of arthritis. Results We sequenced 7,339 mRNAs in total and identified 4,247 different kinds, which were ranked in order of frequency. Fibronectin was the protein most frequently expressed (230/7,339), followed by matrix metalloproteinases (MMPs) 1 and 3. The 9 genes selected were those encoding fibronectin 1, MMP1, MMP3, tissue inhibitor of metalloproteinase 3, apolipoprotein L-I (APOL1), syndecan binding protein, insulin-like growth factor binding protein 5, heat shock protein 90, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5). We investigated expression of these 9 genes in synovium from the 7 individual patients with OA. All 9 genes were expressed in OA and control synovium. Expression of MMP1 mRNA was weak in OA samples, however, while expression of ADAMTS5 and APOL1 mRNAs was weak in the controls and some of the OA samples. Interpretation ADAMTS5 and APOL1 may have important roles in the mechanism of OA. [ABSTRACT FROM AUTHOR]