RESUMEN
OBJECTIVE: Syndecan-1 (SDC-1), a transmembrane heparin sulphate proteoglycan predominantly expressed on epithelial cells, also exists in a soluble form through ectodomain shedding. SDC-1 expression and shedding may be modulated in the inflammatory milieu of primary Sjögren's syndrome (SS). We investigated SDC-1 expression in minor salivary glands (MSGs) and analysed the association between salivary or plasma levels of SDC-1 and clinical parameters in SS. METHOD: We measured salivary and plasma SDC-1 levels via an enzyme-linked immunosorbent assay and assessed the salivary flow rates (SFRs) in 70 patients with SS and 35 healthy subjects. Disease activity indices, serological markers, salivary gland scintigraphy, and MSG biopsy were evaluated in patients with SS. RESULTS: SDC-1 expression was upregulated on ductal epithelial cells in inflamed salivary glands. Salivary SDC-1 levels in patients significantly exceeded those in healthy subjects [median (interquartile range) 49.0 (20.7-79.1) vs 3.7 (1.7-6.3) ng/mL, p < 0.001] and inversely correlated with SFRs (r = -0.358, p = 0.032) and ejection fractions of the parotid (r = -0.363, p = 0.027) and submandibular (r = -0.485, p = 0.002) glands in salivary gland scintigraphy. Plasma SDC-1 levels were significantly correlated with the EULAR Sjögren's Syndrome Disease Activity Index (r = 0.507, p < 0.001) and EULAR Sjögren's Syndrome Patient Reported Index (r = 0.267, p = 0.033). Focus scores were correlated with salivary SDC-1 levels (r = 0.551, p = 0.004). CONCLUSIONS: Salivary and plasma SDC-1 levels may constitute potential biomarkers for salivary gland function and disease activity, respectively, in SS.
Asunto(s)
Síndrome de Sjögren , Sindecano-1/metabolismo , Biomarcadores/análisis , Humanos , Inflamación , Glándulas Salivales/diagnóstico por imagen , Glándulas Salivales Menores/patologíaRESUMEN
OBJECTIVES: Primary cilium is required for mechano-biological signal transduction in chondrocytes, and its interaction with extracellular matrix is critical for cartilage homeostasis. However, the role of cilia-associated proteins that affect the function of cilia remains to be elucidated. Here, we show that Dicam has a novel function as a modulator of primary cilia-mediated Indian hedgehog (Ihh) signaling in chondrocytes. METHODS: Cartilage-specific Dicam transgenic mouse was constructed and the phenotype of growth plates at embryonic day 15.5 and 18.5 was analyzed. Primary chondrocytes and tibiae isolated from embryonic day 15.5 mice were used in vitro study. RESULTS: Dicam was mainly expressed in resting and proliferating chondrocytes of the growth plate and was increased by PTHrP and BMP2 in primary chondrocytes. Cartilage-specific Dicam gain-of-function demonstrated increased length of growth plate in long bones. Dicam enhanced both proliferation and maturation of growth plate chondrocytes in vivo and in vitro, and it was accompanied by enhanced Ihh and PTHrP signaling. Dicam was localized to primary cilia of chondrocytes, and increased the number of primary cilia and their assembly molecule, IFT88/Polaris as well. Dicam successfully rescued the knock-down phenotype of IFT88/Polaris and it was accompanied by increased number of cilia in tibia organ culture. CONCLUSION: These findings suggest that Dicam positively regulates primary cilia and Ihh signaling resulting in elongation of long bone.
Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Regulación del Desarrollo de la Expresión Génica , Placa de Crecimiento/metabolismo , Proteínas Hedgehog/genética , Transducción de Señal/genética , Animales , Moléculas de Adhesión Celular/genética , Proliferación Celular/genética , Células Cultivadas , Condrocitos/metabolismo , Cilios/metabolismo , Modelos Animales de Enfermedad , Ratones , Ratones Transgénicos , Distribución Aleatoria , Sensibilidad y Especificidad , Regulación hacia ArribaRESUMEN
The purpose of this study was to compare the proportion of therapeutic interventions that is supported by scientific evidence between hospital-based and community-based primary care clinics. The study setting is a primary care clinic in university-affiliated tertiary hospital and community-based primary care clinic in a region in Seoul. A retrospective review of patients' medical records was done according to the primary diagnosis and treatment for 890 patients in community-based clinic and 307 in hospital-based clinic. The evidence for the intervention was searched for in Medline (1966-2001) and other evidence-based databases. The evidence was then classified as one of the three categories (i) evidence from randomised controlled trials (RCTs); (ii) convincing non-experimental evidence; and (iii) interventions without substantial evidence. In the hospital-based clinics, out of 356 primary diagnosis and treatment pairs, 59.6% were supported by evidence from at least one RCTs, and 19.4% were supported by convincing non-experimental evidence. In the community-based clinics, 47.1% out of 893 pairs and 10.5% fell into each category. As a result, the proportion of interventions in community settings that were based on evidence meeting our criteria was significantly lower than that of the hospital-based settings. To facilitate evidence-based practice, supportive activity should be focused on the primary care settings based on community where medical practices are less evidence-based.