Journal
JOURNAL OF ORTHOPAEDIC RESEARCH
Volume 40, Issue 10, Pages 2308-2319Publisher
WILEY
DOI: 10.1002/jor.25251
Keywords
collagen; extracellular matrix; mechanics; molecular profiling; proteomics
Categories
Funding
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [P30AR069619, R01AR064216, T32AR007132, TL1TR000138]
- National Institute on Aging [K99AG065495]
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This study investigates the effect of surgical repair on Achilles tendon healing and finds that repaired tendons have inferior mechanical properties and exhibit enriched inflammatory gene signatures, while non-repaired tendons show increased expression of markers associated with tissue development and mechano-activation.
Operative treatment is assumed to provide superior outcomes to nonoperative (conservative) treatment following Achilles tendon rupture, however, this remains controversial. This study explores the effect of surgical repair on Achilles tendon healing. Rat Achilles tendons (n = 101) were bluntly transected and were randomized into groups receiving repair or non-repair treatments. By 1 week after injury, repaired tendons had inferior mechanical properties, which continued to 3- and 6-week post-injury, evidenced by decreased dynamic modulus and failure stress. Transcriptomics analysis revealed >7000 differentially expressed genes between repaired and non-repaired tendons after 1-week post-injury. While repaired tendons showed enriched inflammatory gene signatures, non-repaired tendons showed increased tenogenic, myogenic, and mechanosensitive gene signatures, with >200-fold enrichment in Tnmd expression. Analysis of gastrocnemius muscle revealed elevated MMP activity in tendons receiving repair treatment, despite no differences in muscle fiber morphology. Transcriptional regulation analysis highlighted that the highest expressed transcription factors in repaired tendons were associated with inflammation (Nf kappa b, SpI1, RelA, and Stat1), whereas non-repaired tendons expressed markers associated with tissue development and mechano-activation (Smarca1, Bnc2, Znf521, Fbn1, and Gli3). Taken together, these data highlight distinct differences in healing mechanism occurring immediately following injury and provide insights for new therapies to further augment tendons receiving repaired and non-repaired treatments.
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