Pifithrin-alpha, an inhibitor of p53 transactivation, alters the inflammatory process and delays tendon healing following acute injury
One page on PainSci cites Marsolais 2007: Guide to Repetitive Strain Injuries
original abstract †Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.
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-alpha, on the pathophysiological sequence following collagenase-induced tendon injury. Administration of pifithrin-alpha during the inflammatory phase reduced the accumulation of neutrophils and macrophages by 30 and 40%, respectively, on day 3 postinjury. Pifithrin-alpha failed to reduce the percentage of apoptotic cells following collagenase injection but delayed functional recovery. In uninjured Achilles tendons, pifithrin-alpha increased metalloprotease activity 2.4-fold. Accordingly, pifithrin-alpha reduced the collagen content in intact tendons as well as in injured tendons 7 days posttrauma compared with placebo. The effect of pifithrin-alpha on load to failure and stiffness was also evaluated. The administration of pifithrin-alpha 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-alpha group from day 7 to day 28 compared with placebo. Overall, our results suggest that administration of pifithrin-alpha alters the inflammatory process and delays tendon healing. The present findings also support the concept that p53 can regulate extracellular matrix homeostasis in vivo.
This page is part of the PainScience BIBLIOGRAPHY, which contains plain language summaries of thousands of scientific papers & others sources. It’s like a highly specialized blog. A few highlights:
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