Insulin‐like growth factor‐I improves cellular and molecular aspects of healing in a collagenase‐induced model of flexor tendinitis

Abstract
Flexor tendinitis is a common and debilitating injury of elite and recreational athletes. Healing may be improved through intratendinous injection of insulin‐like growth factor‐I (IGF‐I), which has been shown in vitro to stimulate mitogenesis and enhance tendon matrix production. This study investigated the effects of intratendinous injection of IGF‐I on tendon healing in an equine model of flexor tendinitis. Collagenase‐induced lesions were created in the tensile region of theflexor digitorum superficialistendon of both forelimbs of eight horses. Treated tendons were injected with 2 μg rhIGF‐I intralesionally every other day for 10 injections, while controls received 0.9% NaCl. Tendon fiber deposition and organization were evaluated serially using ultrasonography throughout the 8 week trial period. Following euthanasia, the tendons were harvested and DNA, hydroxyproline, and glycosaminoglycan content determined, mechanical strength and stiffness evaluated, gene expression and spatial arrangement of collagen types I and III assessed by northern blot and in situ hybridization, and tendon fiber architecture assessed by polarized light microscopy. Local soft tissue swelling was reduced in the IGF‐I treated limbs. Similarly, lesion size in IGF‐I treated tendons was smaller 3 and 4 weeks after initiation of treatment. Cell proliferation and collagen content of the IGF‐I treated tendons were increased compared to controls. Mechanically, IGF‐I treated tendons showed a trend toward increased stiffness compared to saline treated controls. Considered together with the decreased soft tissue swelling and improved sonographic healing, these data support the potential use of intralesional IGF‐I for treatment of debilitating tendon injuries.

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