西田 圭一郎

We investigated the presence of osteocyte apoptosis in the necrotic trabeculae of the femoral head of spontaneously hypertensive rat (SHR) using the in situ nick end labeling (TUNEL) method and transmission electron microscopy. The occurrence of osteonecrosis and ossification disturbance was significantly higher in SHR compared with Wistar Kyoto (WKY) rats, and Wistar (WT) rats used as control animals (P < 0.01). A high population of TUNEL positive osteocytes was detected mainly in 10- and 15-week-old SHRs. Sectioned examination of the femoral head of SHRs and WKY rats by electron microscopy revealed apoptotic cell appearances such as aggregation of chromatin particles and lipid formation. In contrast, a positive reaction was significantly lower in osteocytes in the femoral heads of WT rats (P < 0.01). Our results indicate that apoptosis forms an important component of the global pathologic process affecting the femoral head of SHR, which leads to osteonecrosis in this region.

Angiogenesis is an essential event in the development of synovial inflammation in rheumatoid arthritis (RA). The aim of the current study was to investigate the expression of vasohibin-1, a novel endothelium-derived vascular endothelial growth factor (VEGF)-inducible angiogenesis inhibitor, in the RA synovium, and to test the effect of inflammatory cytokines on the expression of vasohibin-1 by RA synovial fibroblasts (RASFs). Synovial tissue samples were obtained at surgery from patients with osteoarthritis (OA) and RA, and subjected to immunohistochemistry to investigate the expression and distribution of vasohibin-1 relevant to the degree of synovial inflammation. In an in vitro analysis, RASFs were used to examine the expression of vasohibin-1 and VEGF mRNA by real-time PCR after stimulation with VEGF or inflammatory cytokines under normoxic or hypoxic conditions. The immunohistochemical results showed that vasohibin-1 was expressed in synovial lining cells, endothelial cells, and synovial fibroblasts. In synovial tissue, there was a significant correlation between the expression of vasohibin-1 and histological inflammation score (p0.002, r0.842). In vitro, stimulation with VEGF induced the expression of vasohibin-1 mRNA in RASFs under normoxic conditions, and stimulation with cytokines induced vasohibin-1 mRNA expression under a hypoxic condition. These results suggest that vasohibin-1 was expressed in RA synovial tissue and might be regulated by inflammatory cytokines.

Mechanical stress plays a key role in the pathogenesis of cartilage destruction seen in osteoarthritis (OA). We investigated the effect of cyclic tensile stress (CTS) on the anabolic and catabolic gene expression of rat cultured normal chondrocytes using the Flexercell strain unit. The effects of interleukin (IL)-4, a chondroprotective cytokine, on the changes in gene expression induced by CTS were also investigated. CTS (7% elongation at 0.5 Hz) for 24 h did not affect the expression of aggrecan and type II collagen, whereas CTS significantly upregulated matrix metalloproteinase (MMP)-13 and cathepsin B mRNA expression by chondrocytes. IL-1beta expression was also signifi cantly upregulated by CTS up to 12 h. The upregulation of MMP-13 was observed at 3 h, which was earlier than that of IL-1beta. Furthermore, pre-treatment with IL-4 (10 ng/ml) suppressed both MMP-13 and cathepsin B induction by mechanical stress, as well as CTS-induced IL-1beta expression. Our results suggest that IL-4 might have a therapeutic value in the treatment of OA by downregulation of mechanical stress-induced MMP-13 and cathepsin B expression by chondrocytes.

Localization of the glycosaminoglycans (GAG) was examined in the synovial membranes of patients with osteoarthritis under light microscopy using a fine cationic colloidal iron staining method combined with enzymatic digestion. Our staining method was very useful for demonstrating the difference in the localization of GAG in regions of the inflammatory site in the osteoarthritic synovial membrane. Hyaluronic acid was mainly located in connective tissues in the surface intercellular and perivascular spaces, chondroitin sulfate A/C in the highly fibrous part of and connective tissue around blood vessels, dermatan sulfate (chondroitin sulfate B) in the subsurface interstitium and vascular endothelial cells and heparan sulfate in part of vascular endothelial cells. No keratan sulfate was detected. GAG is reported to have an important role in cell movement, adherence and aggregation in the inflammatory sites. These findings should be useful for understanding the role of GAG in physiological and pathologic processes of secondary synovitis.

Mast cells in osteoarthritic and rheumatoid arthritic synovial tissues of the human knee.

Instability of the knee after the medial collateral ligament (MCL) injury is usually assessed with the manual valgus stress test, even though, in recent years, it has become possible to apply magnetic resonance imaging (MRI) to the assessment of the damage of the ligament. The valgus instability of 24 patients (12 isolated injuries and 12 multiple ligament injuries) who suffered MCL injury between 1993 and 1998 was evaluated with the Hughston and Eilers classification, which involves radiographic assessment under manual valgus stress to the injured knees. We developed a novel system for classifying the degree of injury to the MCL by calculating the percentage of injured area based on MRI and investigated the relationship between this novel MRI classification and the magnitude of valgus instability by the Hughston and Eilers classification. There was a significant correlation between the 2 classifications (p=0.0006). On the other hand, the results using other MRI based classification systems, such as the Mink and Deutsch classificaiton and the Petermann classification, were not correlated with the findings by the Hughston and Eilers classification in these cases (p0.05). Since MRI is capable of assessing the injured ligament in clinical practice, this novel classification system would be useful for evaluating the stability of the knee and choosing an appropriate treatment following MCL injury.

Sixty-seven trigger fingers of 58 idiopathic and hemodialysis patients were treated by percutaneous A1-pulley release technique. Severity of triggering was classified into five grades for treatment selection and prediction of possible results. Results were excellent in 41 fingers, good in 9, fair in 7, and poor in 10, requiring additional treatment. The results of the lower grades were better, and those of the higher grades were poor. Excellent or good results appeared to depend on the proper selection of the patients according to the grading system and confirmation of triggering disappearance just after the release. There were neither infections nor neuro-vascular deficits after treatment. Compared to conventional open release, this treatment was found to be more useful from the standpoints of ease and safety of the technique, and the patients' quick return to normal life.