Nonsurgical treatment reduces tendon inflammation and elevates tendon markers in early healing. Issue 10 (7th January 2022)

• Record Type: Journal Article
• Authors: Freedman, Benjamin R.; Adu‐Berchie, Kwasi; Barnum, Carrie; Fryhofer, George W.; Salka, Nabeel S.; Shetye, Snehal; Soslowsky, Louis J.
• Is Part Of: Journal of orthopaedic research. Volume 40:Issue 10(2022)
• Page Start: 2308
• Page End: 2319
• Publication Date: 2022-01-07
• Subjects: collagen -- extracellular matrix -- mechanics -- molecular profiling -- proteomics; Orthopedics -- Periodicals; Musculoskeletal system -- Periodicals; 616.7
• DOI: 10.1002/jor.25251
• Languages: English
• ISSNs: 0736-0266

Abstract

Abstract: 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 ( Nfκb, 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. Abstract : This study explored the effect of surgical repair on Achilles tendon healing. Rats received two weeks of treadmill running before tendon injury and division into repaired and non‐repaired groups. Rats then were immobilized for 1‐week and were returned to exercise for 0, 2, or 5 weeks prior to euthanasia and tissue evaluation. By 1 week after injury, repaired tendons had inferior mechanical properties, which continued to 3‐ and 6‐week post‐injury. 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. Analysis of gastrocnemius muscle revealed elevated MMP activity in tendons receiving repair treatment. Transcriptional regulation analysis highlighted that the highest expressed transcription factors in repaired tendons were associated with inflammation ( Nfκb, SpI 1, RelA, and Stat 1), whereas non‐repaired tendons expressed markers associated with tissue development and mechano‐activation ( Smarca 1, Bnc 2, Znf 521, Fbn 1, and Gli 3). Taken together, these data highlight distinct differences in healing mechanism occurring immediately following injury.