Impact of Smad3 Loss of Function on Scarring and Adhesion Formation During Tendon Healing

Overview

Journal J Orthop Res

Publisher Wiley

Specialty Orthopedics

Date 2010 Sep 16

PMID 20842701

Citations 63

Authors

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 OKeefe

Affiliations

Soon will be listed here.

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.

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