Inhibition of TGF-beta-induced collagen production in rabbit flexor tendons.
OBJECTIVE
Postoperative adhesions frequently compromise the success of flexor tendon repair. Manipulation of growth factors responsible for scar formation may be a method of decreasing adhesion formation. Transforming growth factor beta (TGF-beta) is a key cytokine in the pathogenesis of tissue fibrosis. The purpose of this study was to examine the effectiveness of TGF-beta neutralizing antibody in blocking TGF-beta-induced collagen I production in rabbit flexor tendons in vitro.


METHODS
Sheath fibroblasts, epitenon tenocytes, and endotenon tenocytes were obtained from rabbit flexor tendons. Each cell culture was supplemented with 1 ng/mL of TGF-beta along with increasing doses of TGF-beta neutralizing antibody (0.1-2.0 microg/mL). Collagen I production was measured by enzyme-linked immunoabsorbent assay and TGF-beta bioactivity was measured by the luciferase assay. Results were compared with TGF-beta alone and unsupplemented controls.


RESULTS
The addition of neutralizing antibody significantly reduced TGF-beta-induced collagen I production in a dose-dependent manner in all 3 cell cultures. TGF-beta bioactivity was also reduced by its neutralizing antibody.


CONCLUSIONS
This study shows that TGF-beta inhibition through its neutralizing antibody was effective in cultured flexor tendon cells. The results encourage further experiments that use such agents to modulate flexor tendon wound healing in in vivo models in the hope of eventually blocking the effect of TGF-beta on flexor tendons clinically.
Zhang
Andrew Y
AY
Division of Plastic Surgery, Stanford University Medical Center, 770 Welch Road, Stanford, CA 94305, USA.
Pham
Hung
H
Ho
Fred
F
Teng
Kevin
K
Longaker
Michael T
MT
Chang
James
J
D000818:Animals; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D011817:Rabbits; D013708:Tendon Injuries / Q000503:physiopathology; D013710:Tendons / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*; D015854:Up-Regulation; D014945:Wound Healing
D024042:Collagen Type I; D016212:Transforming Growth Factor beta