title: Quantitative and Qualitative Change of Collagen of Achilles Tendons in Rats With Systemic Administration of Glucocorticoids.
abstract: BACKGROUND
  It is unclear whether glucocorticoid (GC) therapy is directly related to Achilles tendon rupture (ATR), because many of the reported patients were receiving long-term GC therapy for underlying diseases. This study aimed to elucidate the mechanism by which systemic GC administration causes weakening of the Achilles tendon by biochemically, mechanically, and morphologically evaluating quantitative and qualitative changes in collagen.
  
  
  METHODS
  Male 8-week-old mice were subcutaneously treated with either prednisolone (10 mg/mL/kg; GC group) or saline (1 mL/kg; control group) for 8 weeks and then subjected to the following experiments: (1) a tensile strength test; (2) quantification of the gene expressions of type 1 collagen and lysyl oxidase; (3) quantification of collagen content, enzymatic crosslinks (immature + mature), and senescent crosslinks; and (4) measurement of collagen fiber diameter by electron microscopy.
  
  
  RESULTS
  The maximum tensile load and gene expressions of type 1 collagen and lysyl oxidase were decreased in the GC group. Collagen content was significantly decreased in the GC group compared with the control group. The content of enzymatic crosslinks was significantly lower in the GC group than in the control group. The corresponding amount of senescent crosslinks was not significantly different. The mean collagen fiber diameter was significantly smaller in the GC group than in the control group. Histogram analysis showed a decreased number of thick fibers and an increased number of thin fibers in the GC group.
  
  
  CONCLUSIONS
  These observations suggest that systemic GC administration causes decreased strength of the Achilles tendon by decreasing its collagen content, hindering the formation of enzymatic crosslinks and thereby keeping collagen fibers in an immature state with smaller diameters.
  
  
  CONCLUSIONS
  This animal study showed that systemic GC administration directly prevents maturation of tendon collagen fibers and decreases tendon strength, regardless of the presence or absence of underlying disease.
authors.affiliation: Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Taguchi
authors.affiliation: Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo, Japan xlink67@gol.com.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Hattori
authors.affiliation: Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Marumo
mesh_terms: D000125:Achilles Tendon / Q000378:metabolism*; D000818:Animals; D003094:Collagen / Q000378:metabolism* / Q000648:ultrastructure; D024042:Collagen Type I / Q000235:genetics; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D008854:Microscopy, Electron; D011239:Prednisolone / Q000494:pharmacology*; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013718:Tensile Strength / Q000187:drug effects
chemical_list: D024042:Collagen Type I; D005938:Glucocorticoids; D003094:Collagen; D011239:Prednisolone; D008249:Protein-Lysine 6-Oxidase
keywords: collagen; crosslink; electron microscope; general administration; glucocorticoid; rat; tensile strength test