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The present system may provide a useful means of phenotypic analysis of genetic information in mammalian organs for basic research as well as therapeutic molecular targeting in the post-genomic era.

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These results suggest that hPDL cells may play a role in the production of cytokines in response to mechanical stress in vivo.

Objective. To deliver and overexpress the hsp70 gene in cultured chondrocytes to investigate its effect on nitric oxide (NO)-induced apoptosis of chondrocytes.Methods. Primary chondrocyte cultures were established from rabbit joints. The cells were transduced with an empty adenovirus vector (Ax1w) or an adenovirus vector harboring the hsp70 E-tag fusion gene (AxSHEwt Degradation of articular cartilage, the major component of a joint, causes serious dysfunction of joints. Osteoarthritis (OA) is associated with degeneration of articular cartilage, but its pathogenesis has not yet been fully elucidated. Various biologic and chemical stress factors are thought to be involved in the occurrence and progression of OA, including mechanical stress, inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor ␣, and reactive oxygen species (ROS) such as nitric oxide (NO). Chondrocytes are responsible for the maintenance of articular cartilage. Reduced cartilage cellularity has been postulated to play a role in the pathogenesis of OA (1,2), and the reduction in cellularity in human OA cartilage is partly attributable to apoptosis, i.e., programmed cell death. Recent studies have shown apoptosis of articular chondrocytes in OA in humans and in experimental animals (3,4), which implies the importance of apoptosis in the progression of the pathology of OA. Thus, apoptosis has attracted the attention of researchers as a potential etiologic factor in OA progression (5). If apoptosis of OA chondrocytes could be controlled, the implications of apoptosis in OA pathogenesis would become clearer, and the suppression method would suggest a novel therapeutic intervention against OA.One of the major cellular responses to stress involves synthesis of a set of highly conserved proteins, called heat-shock proteins (HSPs), during a process referred to as the stress response. In mammalian systems, HSPs include proteins with molecular weights of 110, 90, 70, 60, 40, and 27 kd. Some HSP members are constitutively expressed, and the expression levels increase in response to stress, while others are induced after exposure to stress. HSPs not only protect cells from stress-induced damage, but also facilitate the recovery of cells from the damage by binding to degraded or misfolded polypeptides (6-8). The inducible Hsp70 is a major HSP, and its expression is augmented in OA

This study demonstrated that the treatment of chondrocytes with Gln protected the cells from heat stress and NO-induced apoptosis. These chondroprotective effects of Gln may be mediated by HSP70.

The objective of the present study was to determine whether the expression of connexin 43 (Cx43) effected on inflammatory conditions in rat fibroblast-like synoviocytes (FLS) and on rat model of rheumatoid arthritis (RA). The expression of Cx43 in rat FLS stimulated with lipopolysaccharide (LPS) was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The effects of small-interfering RNA targeting Cx43 (siCx43) on pro-inflammatory cytokines and chemokine were assessed by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA). The therapeutic and side effects of siCx43 in a rat model of collagen-induced arthritis (CIA) were examined by in vivo electroporation method. LPS markedly enhanced Cx43 gene expression in rat FLS, with transfection of siCx43 suppressing the over-expression of pro-inflammatory cytokines and the chemokine. Treatment of CIA rats with siCx43 significantly ameliorated paw swelling, and significantly reduced histological arthritis scores and radiographic scores. In histological appearance of rat ankle joints, siCx43 treatment significantly decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive (osteoclast-like) cells. These findings indicated that siCx43 had anti-inflammatory effects in rat FLS and efficiently inhibited the development of CIA. Cx43 may play an important role in the pathophysiology of RA, and may be a potential target molecule for novel RA therapies. Keywords: connexin 43; gap junction; pro-inflammatory cytokine; rheumatoid arthritis; collagen-induced arthritis Rheumatoid arthritis (RA) is one of the most common articular diseases, characterized by hyperproliferation of synovial cells and bone destruction. Pro-inflammatory cytokines and chemokines, including tumor necrosis factor (TNF)-a, interleukin (IL)-6, IL-1b, and stromal cell-derived factor 1 (CXCL12), have been associated with the progression of RA and may play pathogenic roles in the establishment of rheumatoid synovitis. 1,2Biological preparations targeting these pro-inflammatory cytokines are widely used clinically in the treatment of RA.3 However, there are caveats in using the biological preparations, including risk of infections such as tuberculosis, high cost, and individual variations in efficacy.4 Therefore, further investigations are needed to achieve remission of arthritis.Gap junctions are cell-cell communication channels, consisting of multimeric proteins called connexins, that allow the exchange of ions, second messengers, and metabolites between adjacent cells.5 To date, 21 human genes encoding connexins have been identified. The most widely expressed connexin gene is connexin 43 (Cx43), a protein expressed in the synovial cells and tissue.6 Cx43 plays an important role in the regulation of various immune processes. 7 In the nervous system, silencing of Cx43 downregulates the inflammatory response. 8,9 These reports suggest that Cx43 may be involved in RA pathophysiology, and that inhibition of Cx43 may decrease synovitis in RA.Therefore, we ...

Deep infection associated with implants remains a serious complication of orthopedic surgery. We developed iodine coating for titanium implants. In this study, we performed a clinical trial of iodine-coated megaprostheses to evaluate its safety and antibacterial effects. Forty-seven patients with malignant bone tumor or pyogenic arthritis were treated using iodine-supported titanium megaprostheses between July 2008 and May 2013. The mean age was 53.6 years (range, 15-85 years). Twenty-six patients were males and 21 were females. The diagnoses included malignant bone tumor in 29 cases, infected total knee arthroplasty in 11 cases, chronic osteomyelitis due to pyogenic arthritis in six cases and loosening of total knee arthroplasty in one case. The iodine-supported implants used were 42 Kyocera Limb Salvage System and five KOBELCO K-MAX K-3. These megaprostheses were used to prevent infection in 21 patients, treat active infections in 26 patients. The mean follow-up period was 30.1 months (range, 8-50). Infection was prevented in 20 out of 21 patients. Only one patient had surgical site infection caused by Pseudomonas aeruginosa and was cured by intravenous administration of antibiotics alone without removal of the implant. In 26 treatment cases involving one- or two-stage revision surgery, infection subsided without any additional surgery. In all cases, there were no signs of infection at the time of the last follow-up. White blood cell and C-reactive protein levels returned to normal within four weeks after surgery. To confirm systemic effects of iodine, thyroid hormone levels in the blood were examined. Abnormalities of thyroid gland function were not detected. Loosening of the implants was not observed. Excellent bone ingrowth and ongrowth were found around iodine-supported megaprostheses. The iodine-supported titanium megaprostheses are highly effective and show promise for the prevention and treatment of infections in large bone defects. No cytotoxicity or adverse effects were detected with this treatment.