Impact of Smad3 loss of function on scarring and adhesion formation during tendon healing

Evan B. Katzel, Matthew Wolenski, Alayna E. Loiselle, Patrick Basile, Lisa M. Flick, Howard N. Langstein, Matthew J. Hilton, Hani A. Awad, Warren C. Hammert, Regis J. O'Keefe

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82 Scopus citations

Abstract

Studies were performed evaluating the role of Smad3, a transcription factor mediating canonical TGF-β signaling, on scarring and adhesion formation using an established flexor digitorum longus (FDL) tendon repair model. In unoperated animals the metatarsophalangeal (MTP) range of motion (ROM) was similar in Smad3-/- and wild-type (WT) mice while the basal tensile strength of Smad3-/- tendons was significantly (39%) lower than in WT controls. At 14 and 21 days following repair Smad3-/- MTP ROM reached approximately 50% of the basal level and was twice that observed in WT tendon repairs, consistent with reduced adhesion formation. Smad3-/- and WT maximal tensile repair strength on post-operative day 14 was similar. However, Smad3-/- tendon repairs maximal tensile strength on day 21 was 42% lower than observed in matched WT mice, mimicking the relative decrease in strength observed in Smad3-/- FDL tendons under basal conditions. Histology showed reduced "healing callus" in Smad3-/- tendons while quantitative PCR, in situ hybridization, and immunohistochemistry showed decreased col3a1 and col1a1 and increased MMP9 gene and protein expression in repaired Smad3-/- tendons. Thus, Smad3-/- mice have reduced collagen and increased MMP9 gene and protein expression and decreased scarring following tendon FDL tendon repair.

Original languageEnglish
Pages (from-to)684-693
Number of pages10
JournalJournal of Orthopaedic Research
Volume29
Issue number5
DOIs
StatePublished - May 2011

Keywords

  • Smad3
  • TGF-β
  • adhesions
  • flexor tendon healing
  • matrix metalloproteases

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