ABSTRACT
OBJECTIVE: RNA-binding protein with multiple splicing (RBPMS) has been shown to physically interact with Smads and enhance transforming growth factor-ß (TGF-ß)-mediated Smad2/3 transcriptional activity in mammalian cells. Objective of this study was to examine whether expression of RBPMS is regulated by interleukin-1ß (IL)-1ß and TGF-ß superfamily growth factors and whether expression of RBPMS is altered during aging and experimental osteoarthritis. METHODS: Expression of RBPMS protein was investigated in chondrocyte cell lines of murine (H4) and human (G6) origin using Western blot analysis. Regulation of RBPMS expression in H4 chondrocytes at mRNA level was done by reverse transcriptase-quantitative polymerase chain reaction. Furthermore, characterization of Smad signaling pathways regulating RBPMS expression was performed by blocking studies using small molecule inhibitors or by transfection studies with adenoviral vector constructs (constitutive-active ALK1 and constitutive-active ALK5). Expression of RBPMS in cartilage of different age groups of C57BL/6N mice (6 months and 20 months) and in a surgically induced osteoarthritis (OA) mouse model was analyzed using immunohistochemistry. RESULTS: RBPMS was shown to be expressed in chondrocytes and cartilage of murine, human, and bovine origin. TGF-ß inhibited RBPMS expression while BMP2 and IL-1ß increased its expression. TGF-ß-induced inhibition was blocked by ALK5 inhibitor. Overexpression of ca-ALK1 stimulated RBPMS expression. Moreover, RBPMS expression was found to be reduced with ageing and in OA pathogenesis. CONCLUSIONS: Expression of RBPMS in chondrocytes is regulated by TGF-ß superfamily members and IL-1ß, indicating a counter-regulatory mechanism. Expression of RBPMS, in cartilage and its reduction during ageing and OA might suggest its potential role in the maintenance of normal articular cartilage.
ABSTRACT
BACKGROUND: Liver transplantation was started in our centre as early as 1979. We have studied the clinical outcome of patients surviving longer than 15 years, with special interest for the broad range of comorbidity and the self-perceived quality of life. METHODS: All patients who underwent a liver transplantation at an adult age, between March 1979 and February 1991, and who had survived at least 15 years were eligible for the study. Data were collected from the medical records. Health-related quality of life was assessed using the Six-Dimensional EuroQol test. RESULTS: The five-year survival of patients alive 15 years after transplantation was 78%. Thirty-seven patients are currently alive with a median follow-up of 18.8 years (range 15.0 to 26.8) after transplantation. Comorbidity consists predominantly of overweight (57%), osteoporosis (49%), de novo cancer (38%, mainly skin cancer), hypertension (38%), cardiovascular events (19%), diabetes mellitus (22%), cataract (24%), and renal clearance<50 ml/min (11%). The pattern of comorbidity seems to relate to the type of immunosuppression which consisted mainly of prednisolone and azathioprine. Quality of life was perceived as satisfactory (7 on a scale of 0 to 10). However, about half of the patients reported limitations in the domains mobility, usual activities and pain/discomfort. In addition a minority reported some anxiety or depression. CONCLUSION: The outcome of liver transplantation in this early cohort of patients is fairly good. Improvements may be achieved by adaptations in the immunosuppressive regimen.
