Influence of receptor activator of nuclear factor kappa B ligand, osteoprotegerin and interleukin-33 on bone metabolism in patients with long-standing ulcerative colitis.
BACKGROUND
Ulcerative colitis (UC) is a chronic disease with periods of remission and recurrences. Dysfunction of the local immune response leads to chronic inflammation within the large intestine which triggers morphological changes in the intestinal wall as well as induces the synthesis of numerous factors that have an adverse impact on the bone metabolism. The aim of the study was to determine the expression of RANKL, OPG and IL-33 in mucosal biopsies of UC patients with long disease duration as well as serum level of these cytokines in the context of bone density and bone metabolism.


METHODS
The UC group consisted of 56 patients with average disease duration of 16y. The control group comprised 37 healthy individuals. Local expression of cytokines was assessed in the biopsies of colonic mucosa by the real-time PCR and immunohistochemistry (IHC), and their serum concentration was measured by ELISA.


RESULTS
The increased bone resorption observed in patients with UC was reflected by low bone density and high serum level of C-terminal telopeptide (CTX). Mucosal RANKL expression and serum concentration were similar in UC group and healthy subjects, however, UC patients had higher local expression of OPG and serum OPG concentration. Increased IL-33 gene expression was observed only in UC at the mRNA level. We propose that bone resorption in UC patients despite OPG up-regulation could be caused by IL-33-induced mucosal synthesis of a potent proinflammatory cytokine, such as TNF-α, known as a possible inducer of osteoclastogenesis in the way independent of RANKL.
Department of Histology, Medical University of Gdańsk, Gdańsk, Poland. Electronic address: m.stanislawowski@gumed.edu.pl.
M
M
Stanisławowski
Department of Endocrinology and Internal Diseases, Medical University of Gdańsk, Gdańsk, Poland.
P
P
Wiśniewski
Department of Gastroenterology and Hepatology, Medical University of Gdańsk, Gdańsk, Poland.
M
M
Guzek
Department of Histology, Medical University of Gdańsk, Gdańsk, Poland.
P M
PM
Wierzbicki
Department of Gastroenterology and Hepatology, Medical University of Gdańsk, Gdańsk, Poland.
K
K
Adrych
Department of Gastroenterology and Hepatology, Medical University of Gdańsk, Gdańsk, Poland.
M
M
Smoczyński
Department of Endocrinology and Internal Diseases, Medical University of Gdańsk, Gdańsk, Poland.
K
K
Sworczak
Department of Gastroenterology, Medical University of Lublin, Lublin, Poland.
K
K
Celiński
Department of Histology, Medical University of Gdańsk, Gdańsk, Poland.
Z
Z
Kmieć
D000328:Adult; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D000067596:Interleukin-33; D007378:Interleukins / Q000097:blood / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood / Q000378:metabolism*; D053245:RANK Ligand / Q000097:blood / Q000378:metabolism*
C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human
Bone resorption; C-terminal telopeptide (CTX); Interleukin-33 (IL-33); Osteoprotegerin (OPG); Receptor activator of nuclear factor κB ligand (RANKL); Ulcerative colitis (UC)