| Autor: |
Tashjian RZ; Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, Utah 84108 USA., Zitnay J; Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, Utah 84108 USA., Kazmers NH; Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, Utah 84108 USA., Veerabhadraiah SR; Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, Utah 84108 USA., Zelada AC; Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, Utah 84108 USA., Honeggar M; Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, Utah 84108 USA., Smith MC; Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, Utah 84108 USA., Chalmers PN; Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, Utah 84108 USA., Henninger HB; Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, Utah 84108 USA., Jurynec MJ; Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, Utah 84108 USA.; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, USA.; Department of Biomedical Engineering, University of Utah School of Medicine, Salt Lake City, Utah, USA. |
| Abstrakt: |
The biological factors that affect healing after rotator cuff repair (RCR) are not well understood. Genetic variants in the extracellular matrix protein Tenascin C ( TNC ) are associated with impaired tendon healing and it is expressed in rotator cuff tendon tissue after injury, suggesting it may have a role in the repair process. The purpose of the current study was to determine the role of TNC on tendon healing after RCR in a murine model. The supraspinatus tendon was transected and repaired on the left shoulder of Wild-Type (WT-RCR), Tenascin C null ( Tnc - -RCR) and Tnc heterozygous ( Tnc +/- -RCR) mice. Controls included the unoperated, contralateral shoulder of WT-RCR, Tnc - RCR, Tnc +/- -RCR mice and unoperated shoulders from age and genotype matched controls. We performed histologic, activity testing, RNA-seq, and biomechanical analyses. At 8-weeks post-RCR, Tnc - and Tnc +/- mice had severe bone and tendon defects following rotator cuff repair. Tnc - -RCR mice had reduced activity after rotator cuff repair including reduced wheel rotations, wheel duration, and wheel episode average velocity compared with WT-RCR. Loss of Tnc following RCR altered gene expression in the shoulder, including upregulation of sex hormone and WNT pathways and a downregulation of inflammation and cell cycle pathways. Tnc - mice had similar biomechanical properties after repair as WT. Further research is required to evaluate tissue specific alterations of Tnc , the interactions of Tnc and sex hormone and inflammation pathways as well as possible adjuvants to improve enthesis healing in the setting of reduced TNC function. |
