Regulation of Joint Destruction and Inflammation by P53 in Collagen-induced Arthritis

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2002 Jan 12

PMID 11786406

Citations 64

Authors

Yuji Yamanishi

David L Boyle

Michael J Pinkoski

Artin Mahboubi

Tesu Lin

Zuoning Han

Nathan J Zvaifler

Douglas R Green

Gary S Firestein

Affiliations

Soon will be listed here.

Abstract

The role of the tumor suppressor p53 as a key regulator of inflammation was examined in murine collagen-induced arthritis (CIA), a model of rheumatoid arthritis. Wild-type DBA/1 mice develop progressive arthritis in this model, in which p53 expression and apoptosis are evident in the synovial cells. In contrast, the joints of p53(-/-) DBA/1 animals with CIA showed increased severity of arthritis using clinical and histological scoring methods with almost no apoptosis. Consistent with this, collagenase-3 expression and cytokine production (interleukin-1 and interleukin-6) in the joints of p53(-/-) mice with CIA were significantly greater than in wild-type mice. Anti-collagen antibody titers, however, were not different. Therefore, p53 expression occurs during inflammation and acts to suppress local inflammatory responses. Because mutations in p53 have been described in the synovial membrane of rheumatoid arthritis patients, the loss of p53 function in synoviocytes or other cells in the joint because of dominant-negative mutations might contribute to invasion and destruction of the joint in this disease.

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