HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/R321    most recent 00411.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Marsolais, D. Articles by Frenette, J. Search for Related Content PubMed PubMed Citation Articles by Marsolais, D. Articles by Frenette, J.

INFLAMMATION AND CYTOKINES

Pifithrin-, an inhibitor of p53 transactivation, alters the inflammatory process and delays tendon healing following acute injury

¹CRML, CHUL Research Center and ²Department of Rehabilitation, Faculty of Medicine, Université Laval, Quebec City, Quebec, Canada; and ³The Scripps Research Institute, La Jolla, California

Submitted 9 June 2005 ; accepted in final form 14 July 2006

Transcription factor p53, which was initially associated with cancer, has now emerged as an important regulator of inflammation and extracellular matrix homeostasis, two processes highly relevant to tendon repair. The goal of this study was to evaluate the effect of a p53 transactivation inhibitor, namely, pifithrin-, on the pathophysiological sequence following collagenase-induced tendon injury. Administration of pifithrin- during the inflammatory phase reduced the accumulation of neutrophils and macrophages by 30 and 40%, respectively, on day 3 postinjury. Pifithrin- failed to reduce the percentage of apoptotic cells following collagenase injection but delayed functional recovery. In uninjured Achilles tendons, pifithrin- increased metalloprotease activity 2.4-fold. Accordingly, pifithrin- reduced the collagen content in intact tendons as well as in injured tendons 7 days posttrauma compared with placebo. The effect of pifithrin- on load to failure and stiffness was also evaluated. The administration of pifithrin- during the inflammatory phase did not significantly decrease the functional deficit 3 days posttrauma. More importantly, load to failure and stiffness were significantly decreased in the pifithrin- group from day 7 to day 28 compared with placebo. Overall, our results suggest that administration of pifithrin- alters the inflammatory process and delays tendon healing. The present findings also support the concept that p53 can regulate extracellular matrix homeostasis in vivo.

inflammation; collagen; apoptosis