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BMP-6 and BMP-7 accelerate healing in a rat model of inflammatory bowel disease

Several BMPs and their receptors are expressed in the gastrointestinal tract during defelopment and in postnatal life. In the present study, we evaluated the efficacy of BMP-6 and BMP-7 in reducing mucosal damage in a hapten-induced rat model of colitis initiated by the intracolonic administration of the hapten 2,4,6-trinitrobenzensulfonic acid in 30% ethanol. Rats were treated sysstemically by recombinant human BMP-6 (30, 100, and 300 g/kg) or BMP-7 (30, 100, and 250 g/kg) for 2 weeks following injury. Treatment was initiated 24 hours adfter inducing colitis and then on day 2, 3, 5, 7, and 10 thereafter. Control rats were injected with vehicle buffer. Animals were sacrificed 2 weeks after induction of TNSB/etanol colitis and an 8 cm long distal colonic segment was resected and evaluated macroscopically, microscopically, histomorphometrically, and immunohistochemically. The results demonstrate that both BMP-6 ang BMP-7 reduced necrosis and ulcerations by 70-90%. In addition, significant reduction of cell proliferation in the basal segment of colorectal crypts was observed in BMP treated rats. Histomorphometrically, treatment with BMP-7 reduced colon wall thickness as well as accumulation of neutrophils as compared to control rats. Immunohistochemically, BMP-7 was demonstrated in the smooth muscle cells of muscularis propria and muscularis mucosae, both in BMP-6 treated and control rats, while no staining was found in rats treated with BMP-7. These results suggest that systemic administration of BMP-6 of BMP-7 significantly accelerated the healing of colon ulcers and reduced colon inflammation in TNBS/ethanol induced colitis. Keywords: bone morphogenetic proteins, colitis, trinitrobenzene sulfonic acid, animal.

Bone morphogenetic proteins; colitis; trinitrobenzene sulfonic acid; animal

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