Inhibition of cell migration from tendon explants into fibrin clots by extracts derived from cheese whey is largely due to transforming growth factor-beta

Whey-derived growth factor extract (WGFE) and the acid-activated form (WGFE-a) were tested for their ability to influence the migration of cells from chicken flexor tendon biopsies into fibrin clots. When added to the medium surrounding clots, both extracts significantly inhibited migration relative to controls (P < 0.05) in a dose-dependent manner when measurements were made after seven days of incubation. WGFE-a was approximately ten times more potent than WGFE. Since transforming growth factor (TGF)-beta1 and -beta2 activity of WGFE-a is much higher than in WGFE we hypothesized that TGF-beta was responsible for the inhibition of tendon cell migration. Neutralizing anti-TGF-beta monoclonal antibody was added to the medium bathing tendon biopsies in fibrin clots along with WGFE-a. WGFE-a alone inhibited migration by 51% and this was reversed by the antibody in a dose-dependent manner. Furthermore, recombinant human TGF-beta1 and -beta2 significantly inhibited tendon cell migration with similar dose-dependent potency when tested in the assay. These results indicate that TGF-beta is largely responsible for the inhibition of tendon cell migration by WGFE-a. This sheds further light on the functions of this growth factor during the early events in tendon repair. (C) 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.