engleski

Expression of bone morphogenetic protein-2 and -7 during experimental inflammatory bowel disease

Osteoinductive bone morphogenetic proteins such as BMP-2 and BMP-7, along with their osteogenic function, play important role in development and healing of different organs. The recent findings of BMP expression in developing and adult intestine as well as BMP receptor IA and Smad4 mutations in colonic diseases suggest on importance of BMPs in the proliferation and differentiation of colonic cells. The aim of our study is to reveal expression of BMP-2 and BMP-7 during experimental inflammatory bowel disease (IBD) in rats. Although BMP-2 and BMP-7 are different molecules, as the member of BMP family, they showed homology in structure and similarity in activity after clinical applications. We investigated the expression of BMP-2 and BMP-7 in colon tissue during acute and chronic phases of experimental inflammatory disease as well as after 14th day of BMP-7 treatment. Colonic damage was induced by the intracolonical administration of the hapten 2, 4, 6-trinitrobenzensulfonic acid (TNBS) in 30% ethanol. Rats were treated systemically by recombinant human BMP-7 for 2 weeks following injury. Treatment was initiated 24 hours after inducing colitis and then on day 2, 3, 5, 7, and 10 thereafter. Immunolocalisation of BMP-2 and -7 was performed using BMP-2 and -7 goat polyclonal antibody (Santa Cruz, CA, USA). Our immunohistochemical studies in rat colon showed strong staining with BMP-2 and -7 antibodies in rat colon samples. In acute phase of colitis (2nd and 5th day after colitis induction) the pattern of BMP-2 and -7 expressions was similar. The positive BMP staining was predominately located in damaged mucosa of ulcer region. Conversely, during chronic phase (14th and 30th day after colitis induction) BMP-2 and BMP-7 showed different pattern of expression. The BMP-7 expression was mostly placed in the colonocytes along the crypt while BMP-2 is expressed in the colonocytes at the intercrypt table. BMP-7 treatment significantly reduced the expression of both BMP-2 and -7. Different pattern of BMP-2 and -7 expressions during experimental IBD suggest on the important role of BMPs in control the damage progression of colon cells during disease.

bone morphohenetic protein-2; bone morphogenetic protein-7; experimental inflammatory bowel disease; immunohistochemistry

DOI: 10.1007/s00223-007-9018-0