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

• Published in: Journal of orthopaedic research Vol. 20; no. 5; pp. 910 - 919
• Main Authors: Dahlgren, Linda A, van der Meulen, Marjolein C.H, Bertram, John E.A, Starrak, Greg S, Nixon, Alan J
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Ltd 01.09.2002; Wiley Subscription Services, Inc., A Wiley Company; Blackwell Publishing Ltd
• Subjects: Animals; Blotting, Northern - veterinary; Collagen - genetics; Collagen - metabolism; Collagenases - adverse effects; Disease Models, Animal; Female; Horse Diseases - chemically induced; Horse Diseases - drug therapy; Horse Diseases - pathology; Horses; IGF-I; In Situ Hybridization - veterinary; Injections, Intralesional; Insulin-Like Growth Factor I - administration & dosage; Male; Repair; RNA, Messenger - metabolism; Stress, Mechanical; Tendinopathy - chemically induced; Tendinopathy - drug therapy; Tendinopathy - pathology; Tendinopathy - veterinary; Tendon; Tendon Injuries - chemically induced; Tendon Injuries - drug therapy; Tendon Injuries - pathology; Tendon Injuries - veterinary; Tendons - diagnostic imaging; Tendons - drug effects; Tendons - pathology; Tendons - physiopathology; Ultrasonography; Wound Healing - drug effects; Wound Healing - physiology; Model; IGF-I; Repair; Tendon
• ISSN: 0736-0266; 1554-527X
• DOI: 10.1016/S0736-0266(02)00009-8

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 the flexor digitorum superficialis tendon 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.