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Effects of interleukin-6 and interleukin-1 beta on expression of growth differentiation factor-5 and Wnt signaling pathway genes in equine chondrocytes

Artikel i vetenskaplig tidskrift
Författare E. Svala
Anna Thorfve
C. Ley
Helena Barreto Henriksson
J. M. Synnergren
Anders Lindahl
S. Ekman
E. S. R. Skioldehrand
Publicerad i American Journal of Veterinary Research
Volym 75
Nummer/häfte 2
Sidor 132-140
ISSN 0002-9645
Publiceringsår 2014
Publicerad vid Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin
Institutionen för kliniska vetenskaper, Avdelningen för biomaterialvetenskap
Sidor 132-140
Språk en
Länkar dx.doi.org/10.2460/ajvr.75.2.132
Ämnesord HUMAN ARTICULAR CHONDROCYTES, BONE MORPHOGENETIC PROTEINS, TUMOR-NECROSIS-FACTOR, BETA-CATENIN, SYNOVIAL-FLUID, WNT/BETA-CATENIN, IN-VITRO, BINDING PROTEIN, JOINT FORMATION, CARTILAGE, OL RR, 1990, VETERINARY CLINICS OF NORTH AMERICA-EQUINE PRACTICE, V6, P1
Ämneskategorier Klinisk medicin

Sammanfattning

Objective-To determine the effects of interleukin (IL)-6 and IL-1 beta stimulation on expression of growth differentiation factor (GDF)-5 and Wnt signaling pathway genes in equine chondrocytes. Sample-Macroscopically normal articular cartilage samples from 6 horses and osteochondral fragments (OCFs) from 3 horses. Procedures-Chondrocyte pellets were prepared and cultured without stimulation or following stimulation with IL-6 or IL-1 beta for 1, 2, 12, and 48 hours; expression of GDF-5 was determined with a quantitative real-time PCR assay. Expression of genes in various signaling pathways was determined with microarrays for pellets stimulated for 1 and 2 hours. Immunohistochemical analysis was used to detect GDF-5, glycogen synthase kinase 3 beta (GSK-3 beta), and beta-catenin proteins in macroscopically normal cartilage samples and OCFs. Results-Chondrocytes stimulated with IL-6 had significantly higher GDF-5 expression within 2 hours versus unstimulated chondrocytes. Microarray analysis of Wnt signaling pathway genes indicated expression of GSK-3 beta and coiled-coil domain containing 88C increased after 1 hour and expression of beta-catenin decreased after 2 hours of IL-6 stimulation. Results of immunohistochemical detection of proteins were similar to microarray analysis results. Chondrocytes in macroscopically normal articular cartilage and OCFs had immunostaining for GDF-5. Conclusion and Clinical Relevance-Results indicated IL-6 stimulation decreased chondrocyte expression of the canonical Wnt signaling pathway transactivator beta-catenin, induced expression of inhibitors of the Wnt pathway, and increased expression of GDF-5. This suggested IL-6 may inhibit the Wnt signaling pathway with subsequent upregulation of GDF-5 expression. Anabolic extracellular matrix metabolism in OCFs may be attributable to GDF-5 expression. This information could be useful for development of cartilage repair methods.

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