The role of transforming growth factor β (TGF-β) in tendon healing is still not clearly established. TGF-β affects gene expression primarily through the activation of the Smad signaling pathway. The first step in the Smad pathway is the expression of TGF-β inducible early gene (TIEG). Recently, a TIEG knockout mouse has been developed. The purpose of this study was to examine the healing potential of flexor tendons in mice lacking the TIEG gene, and to further examine what role the TIEG pathway plays in flexor tendon repair. Twenty-two mice, consisting of 11 normal wild-type mice and 11 TIEG knockout mice, were euthanized at 8 to 12 weeks of age. The second through fifth FDL tendons of both hind feet were transacted and repaired in zone 2. The repaired tendons were removed from the mice and placed into tissue culture. Tendons were then examined at days 3, 7, 14, 21, and 42 after surgery. Hematoxylin and eosin (HE) staining and immunohistochemical staining for TGF-β, collagen type I, and collagen type III were performed. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to examine expression of TGF-β1, β2, β3, and collagen type I and III. At 42 days after surgery, HE staining showed coaptation of lacerated tendon ends in both groups. Both groups showed healing of the lacerated tendon, but the chronologic expression pattern of TGF-β was different between the knockout and normal tendons. TIEG deficient tendons had delayed expression of TGF-β when compared with control tendons. The collagen mRNA expression pattern was similar with both groups, but the expression level was different, with TIEG knockout tendons having a lower expression of collagen type I mRNA (p < 0.001). TGF-β is thought to play a major role in tendon healing. Healing of tendons in the TIEG knockout mouse suggests the possibility of tendon healing in the absence of the Smad pathway. The knockout mouse model described in the present study provides a novel means for further understanding of the tendon healing process through isolated deletion of specific growth factors.
- Flexor tendon
- Tendon healing
ASJC Scopus subject areas
- Orthopedics and Sports Medicine