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

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. Copyright © 2010 Orthopaedic Research Society.