title: Effects of beta-aminopropionitrile on equine tendon metabolism in vitro and on effects of insulin-like growth factor-I on matrix production by equine tenocytes.
abstract: OBJECTIVE
  To investigate effects of beta-aminopropionitrile and a combination of insulin-like growth factor (IGF)-I and beta-aminopropionitrile on metabolism of equine tendon fibroblasts.
  
  
  METHODS
  Flexor tendon explants from 3 horses.
  
  
  METHODS
  Explants received 1 of 4 treatments (control, IGF-I, beta-aminopropionitrile, and IGF-I/beta-aminopropionitrile) for 10 days, and message expression for collagen types I and III was assessed by use of in situ hybridization. Histologic findings, new protein production, and quantitative determinations of glycosaminoglycan, DNA, and de novo collagen synthesis were made.
  
  
  RESULTS
  Insulin-like growth factor-I stimulated an anabolic response in tendon. Collagen synthesis and glycosaminoglycan and DNA content of explants were all increased. Beta-aminopropionitrile significantly suppressed collagen synthesis, which was not ameliorated by concurrent IGF-I treatment. Beta-aminopropionitrile caused alterations in cell morphology characterized by large round cells with eccentric nuclei and decreased density of collagen fibers. Protein production and collagen type-III mRNA expression were reduced in these cells.
  
  
  CONCLUSIONS
  Treatment with beta-aminopropionitrile resulted in decreased production of protein and collagen synthesis, which could be expected to suppress tendon healing. The negative effects of beta-aminopropionitrile could not be abrogated by addition of IGF-I to the medium. Treatment resulted in alterations in cell morphology and matrix consistency, which could further delay tendon healing. Beta-aminopropionitrile may impair tendon healing at a cellular level by decreasing collagen production or increasing rate of degradation of existing matrix. Because of reduced crosslinking during beta-aminopropionitrile treatment, in combination with transiently decreased tensile strength, alterations in collagen content and structure may weaken the healing tendon.
authors.affiliation: Comparative Orthopaedics Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Dahlgren
authors.forename: A J
authors.initials: AJ
authors.lastname: Nixon
authors.forename: B D
authors.initials: BD
authors.lastname: Brower-Toland
mesh_terms: D000629:Aminopropionitrile / Q000494:pharmacology*; D000818:Animals; D024042:Collagen Type I / Q000096:biosynthesis; D024061:Collagen Type III / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006651:Histocytochemistry / Q000662:veterinary; D006734:Horse Diseases / Q000378:metabolism; D006736:Horses / Q000378:metabolism*; D017403:In Situ Hybridization / Q000662:veterinary; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D052256:Tendinopathy / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary; D013710:Tendons / Q000187:drug effects* / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D000629:Aminopropionitrile; D007334:Insulin-Like Growth Factor I