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Tendon mineralization is progressive and associated with deterioration of tendon biomechanical properties, and requires BMP-Smad signaling in the mouse Achilles tendon injury model.

ABSTRACT: Ectopic tendon mineralization can develop following tendon rupture or trauma surgery. The pathogenesis of ectopic tendon mineralization and its clinical impact have not been fully elucidated yet. In this study, we utilized a mouse Achilles tendon injury model to determine whether ectopic tendon mineralization alters the biomechanical properties of the tendon and whether BMP signaling is involved in this condition. A complete transverse incision was made at the midpoint of the right Achilles tendon in 8-week-old CD1 mice and the gap was left open. Ectopic cartilaginous mass formation was found in the injured tendon by 4weeks post-surgery and ectopic mineralization was detected at 8 to 10weeks post-surgery. Ectopic mineralization grew over time and volume of the mineralized materials of 25-weeks samples was about 2.5 fold bigger than that of 10-weeks samples, indicating that injury-induced ectopic tendon mineralization is progressive. In vitro mechanical testing showed that max force, max stress and mid-substance modulus in the 25-weeks samples were significantly lower than the 10-weeks samples. We observed substantial increases in expression of bone morphogenetic protein family genes in injured tendons 1week post-surgery. Immunohistochemical analysis showed that phosphorylation of both Smad1 and Smad3 was highly increased in injured tendons as early as 1week post-injury and remained high in ectopic chondrogenic lesions 4-weeks post-injury. Treatment with the BMP receptor kinase inhibitor (LDN193189) significantly inhibited injury-induced tendon mineralization. These findings indicate that injury-induced ectopic tendon mineralization is progressive, involves BMP signaling and associated with deterioration of tendon biomechanical properties.

SUBMITTER: Zhang K

PROVIDER: S-EPMC4875838 | biostudies-literature | 2016 May-Jul

REPOSITORIES: biostudies-literature

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Tendon mineralization is progressive and associated with deterioration of tendon biomechanical properties, and requires BMP-Smad signaling in the mouse Achilles tendon injury model.

Zhang Kairui K Asai Shuji S Hast Michael W MW Liu Min M Usami Yu Y Iwamoto Masahiro M Soslowsky Louis J LJ Enomoto-Iwamoto Motomi M

Matrix biology : journal of the International Society for Matrix Biology 20160126

Ectopic tendon mineralization can develop following tendon rupture or trauma surgery. The pathogenesis of ectopic tendon mineralization and its clinical impact have not been fully elucidated yet. In this study, we utilized a mouse Achilles tendon injury model to determine whether ectopic tendon mineralization alters the biomechanical properties of the tendon and whether BMP signaling is involved in this condition. A complete transverse incision was made at the midpoint of the right Achilles tend ...[more]

PMID: 26825318

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Project description:BackgroundPercutaneous repair of acute Achilles tendon rupture (ATR) continues to gain in popularity. The primary aim of the study was to review the outcomes of a patient cohort undergoing a novel technique of endoscopic percutaneous Achilles tendon repair with absorbable suture. A secondary purpose of this study was to evaluate the basic biomechanical properties of the technique.MethodsA cohort of 30 patients who underwent percutaneous ATR repair was retrospectively analyzed with Achilles Tendon Rupture Scores (ATRS), complications, and additional outcome measures. For a biomechanical analysis portion of the study, 12 cadaveric specimens were paired and randomized to either novel percutaneous repair or open Kessler repair with absorbable suture. These specimens were subjected to 2 phases of cyclical testing (100 cycles 10-43 N followed by 200 cycles 10-86 N) and ultimate strength testing.ResultsIn the clinical portion of the study we report excellent patient reported outcomes (mean ATRS 94.1), high level of return to sport, and high patient satisfaction. One partial re-rupture was reported but with no major wound or neurologic complications. In the biomechanical portion of the study we found no significant difference in tendon gapping between percutaneous and open repairs in phase 1 of testing. In phase 2, increased gapping occurred between percutaneous (17.8 mm [range 10.7-24.1, SD 6.4]) and open repairs (10.8 mm [range 7.6-14.9, SD 2.7, P = .037]). The ultimate load at failure was not statistically different between the 2 repairs.ConclusionsA percutaneous ATR repair technique using endoscopic assistance and absorbable suture demonstrated low complications and good outcomes in a cohort of patients, with high satisfaction, and excellent functional outcomes including high rates of return to sport. Cadaveric biomechanical testing demonstrated excellent survival during testing and minimal increase in gapping compared with open repair technique, representing sufficient strength to withstand forces seen in early rehabilitation. A percutaneous Achilles tendon repair technique with absorbable suture may minimize risks associated with operative repair while still maintaining the benefit of operative repair.Level of evidenceLevel IV, retrospective case series.

Dataset Information

Tendon mineralization is progressive and associated with deterioration of tendon biomechanical properties, and requires BMP-Smad signaling in the mouse Achilles tendon injury model.

Publications

Tendon mineralization is progressive and associated with deterioration of tendon biomechanical properties, and requires BMP-Smad signaling in the mouse Achilles tendon injury model.

Similar Datasets

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