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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Katzel, EB; Wolenski, M; Loiselle, AE; Basile, P; Flick, LM; Langstein, HN; Hilton, MJ; Awad, HA; Hammert, WC; O'Keefe, RJ

Published Date

  • May 2011

Published In

Volume / Issue

  • 29 / 5

Start / End Page

  • 684 - 693

PubMed ID

  • 20842701

Electronic International Standard Serial Number (EISSN)

  • 1554-527X

International Standard Serial Number (ISSN)

  • 0736-0266

Digital Object Identifier (DOI)

  • 10.1002/jor.21235

Language

  • eng