engleski

Expression of RANKL/RANK/OPG in colon during experimental inflammatory bowel disease

INTRODUCTION: RANKL/RANK/OPG system has key role in bone metabolism. Beyond its role in bone loss, it was also documented their importance during inflammation which is occurred in inflammatory bowel disease (IBD). The aim of this study was to investigate the expression of receptor activator of NF-B ligand (RANKL) and its receptors RANK as well its decoy receptor osteoprotegerin (OPG) in colon during experimantal IBD and following BMP7 or corticosteroid therapy. METHODS/DESIGN: IBD was induced by intrarectal administration of trinitrobenzenesulfonic acid (TNBS). After the IBD induction, the rats were treated with BMP-7 (100 g/ml) and sacrificed on the 2nd, 5th, 14th, and 30th day after the TNBS induction. The presence of RANKL, RANK and OPG in inflammatory bowel disease was determined by the continuous monitoring of the expression level of in rat colons during different phases of experimental IBD as well as after BMP7 treatment. An expression level of OPG was determined by RT-PCR and immunohistochemical analyses. Additionally, to investigate the influence of corticosteroid therapy on RANKL/RANK/OPG expression, we treated the diseased animals by 2 mg/kg of dexamethasone during 5 days. RESULTS: During IBD the expression of RANKL/RANK/OPG system was found in all colon samples. The expression level of OPG increased with disease duration and showed the largest expression on 30th day of colitis which is opposite to expression level of RANK which expression decreased according to disease duration. BMP7 therapy as well as ethanol control showed no significant difference in their expression levels compared with diseased animals. Immunohistocemical analysis revealed the presence of OPG in epithelial cells and in limphoid infilration. RANKL expression was also detected in colon samples with increased expression after corticosteroid therapy. CONCLUSION: The expression pattern of all components of RANKL/RANK/OPG system during IBD suggests on their important role in inflammation and probably on bone loss associated with IBD.

RANKL; RANK; osteoprotegerin; inflammatory bowel disease; TNBS colitis

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