title: 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 superficialis tendon of both forelimbs of eight horses. Treated tendons were injected with 2 microg rhlGF-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.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Veterinary Medical Center, Ithaca, NY 14853, USA.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Dahlgren
authors.forename: Marjolein C H
authors.initials: MC
authors.lastname: van der Meulen
authors.forename: John E A
authors.initials: JE
authors.lastname: Bertram
authors.forename: Greg S
authors.initials: GS
authors.lastname: Starrak
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Nixon
mesh_terms: D000818:Animals; D015152:Blotting, Northern / Q000662:veterinary; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D017364:Collagenases / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D006734:Horse Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D006736:Horses; D017403:In Situ Hybridization / Q000662:veterinary; D015552:Injections, Intralesional; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D013314:Stress, Mechanical; D052256:Tendinopathy / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D013708:Tendon Injuries / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D013710:Tendons / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D014463:Ultrasonography; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D017364:Collagenases