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Osteopontin Ablation Attenuates Progression of Colitis in TNBS Model

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Abstract

Introduction

OPN has been implicated in the inflammatory response to Crohn’s disease. We hypothesized that OPN deficiency protects against different stages of TNBS-induced colitis in a modified model that mimics Crohn’s disease.

Material and Methods

OPN-deficient and wildtype mice were treated intracolonically with TNBS and euthanized during acute, sub-acute and chronic colitis.

Results

TNBS-treated wildtype mice developed severe colitis, but OPN-deficient mice were significantly protected. Wildtype mice showed significant infiltration of inflammatory cells including macrophages, and colonic transmural thickening that progressed to strictures, increased matrix collagen deposits (X2 fold), and granuloma formation. These pathological findings were partially attenuated by OPN deficiency. The inflammatory marker, serum amyloid A (SAA), markedly increased in sub-acute stages regardless of OPN status. Conversely, OPN deficiency significantly reduced concentration of SAA in the acute and chronic stages. Secretory OPN was upregulated particularly in acute stage in wildtypes (P < 0.001) and as expected not present in OPN-deficient animals. Flow cytometry analysis of splenic macrophages revealed significant increases in scavenger receptors, macrosialin and F4/80 markers’ expression in wildtypes.

Conclusions

Our data support the role of OPN in induction of inflammation and establishment of chronic colitis. Therefore, OPN may represent a target for therapeutic intervention in Crohn’s disease.

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Abbreviations

DSS:

Dextran sodium sulfate

FITC:

Fluorescein isothiocyanate

IBD:

Inflammatory bowel disease

OPN:

Osteopontin

PE:

Phycoerythrin, labeled

SAA:

Serum amyloid A

SR-A:

Scavenger receptor class A

TNBS:

Trinitrobenzene sulfonic acid

WT:

Wildtype

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Acknowledgments

This research was partially supported by the National Institutes of Health grants: NCCAM-AT1490 and NIDCR-DE19177 (HO). This study was presented in part as a poster of distinction at the Digestive Disease Week 2008 in San Diego, CA (Gastroenterology Suppl 2008:134,A-525,T1296).

Conflict of interest

There is no conflict of interest.

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Authors and Affiliations

  1. Department of Physiology, University of Kentucky Medical Center, MS-507, 800 Rose St, Lexington, KY, 40515-0298, USA

    Helieh S. Oz

  2. Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY, USA

    Helieh S. Oz, Jian Zhong & Willem J. S. de Villiers

  3. Division of Digestive Diseases and Nutrition, University of Kentucky Medical Center, Lexington, KY, USA

    Jian Zhong & Willem J. S. de Villiers

Authors
  1. Helieh S. Oz
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  2. Jian Zhong
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  3. Willem J. S. de Villiers
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Correspondence to Helieh S. Oz.

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Oz, H.S., Zhong, J. & de Villiers, W.J.S. Osteopontin Ablation Attenuates Progression of Colitis in TNBS Model. Dig Dis Sci 57, 1554–1561 (2012). https://doi.org/10.1007/s10620-011-2009-z

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  • DOI: https://doi.org/10.1007/s10620-011-2009-z

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