he treatment of overuse
tendon injuries with exogenous
growth factors such as
insulin-like growth factor-I (
IGF-I) may facilitate an improved return to sustained athletic function. The
biological effects of
IGF-I are exerted under the control of a complex of IGF receptors,
binding proteins, and
proteases. This IGF system includes a family of six structurally related high-affinity
IGF binding proteins (IGFBPs) that protect
IGF-I from local
proteases and restrict access of
IGF-I to its receptor. This study describes the expression of the IGFBPs in flexor tendon after acute injury and during healing over time.
Collagenase-induced lesions were created in the tensile region of the flexor digitorum superficialis tendon of both forelimbs of 14 horses. Tendons were harvested from euthanatized horses 1, 2, 4, 8, or 24 weeks following injury. Gene expression was quantitated by fluorescent real-time PCR, and
protein expression was evaluated by Western
ligand blot (WLB). Message for IGFBPs 2 to 6 was expressed in both normal and healing tendon. No
IGFBP-1 mRNA was detected in equine tendon. Message expression for
IGFBP-2, -3, and -4 increased following injury, whereas message expression for
IGFBP-5 and -6 decreased.
Protein expression for
IGFBP-2, -3, and -4 was detected by WLB in normal tendon and showed a marked increase following injury.
Protein for
IGFBP-5 and -6 was not detectable by WLB in normal or healing tendon. The results of this study document the
IGFBP response of flexor tendons to injury and healing, which provides information necessary for the design of protocols that may enhance tendon healing through manipulation of
IGF-I ligand and
binding protein levels.