title: Contribution of oxidative stress to the degeneration of rotator cuff entheses.
abstract: BACKGROUND
  Rotator cuff degeneration is one of the multiple factors that lead to rotator cuff tears; however, the precise mechanism of such degeneration still remains unclear. In this study, we investigated the supraspinatus tendon enthesis to clarify the link between rotator cuff degeneration and oxidative stress in antioxidant enzyme superoxide dismutase 1 (Sod1)-deficient mice (Sod1(-/-)).
  
  
  METHODS
  The supraspinatus tendon and humeral head were isolated and fixed to prepare histologic sections from wild-type and Sod1(-/-) male mice at 20 weeks of age. Hematoxylin-eosin staining was performed to assess the histomorphologic structure. To investigate the collagen fibers, we examined spatially aligned collagen fibers using a polarizing microscope and assessed the amount of collagen using immunohistochemical staining. To analyze the tissue elasticity, we measured the tissue acoustic properties using scanning acoustic microscopy.
  
  
  RESULTS
  The Sod1(-/-) mice showed histologic changes, such as a misaligned 4-layered structure and fragmented tidemark, in the enthesis. Sod1 loss also decreased the amount of brightly diffracted light and type I collagen, indicating collagen downregulation. The scanning acoustic microscopy analysis showed that the speed and attenuation of sound were increased in the nonmineralized fibrocartilage of the Sod1(-/-) mice, suggesting decreased mechanical properties in the supraspinatus enthesis.
  
  
  CONCLUSIONS
  Sod1 deficiency-induced degeneration is associated with impaired elasticity in the supraspinatus tendon enthesis, recapitulating human rotator cuff degeneration. These results suggest that intracellular oxidative stress contributes to the degeneration of rotator cuff entheses.
authors.affiliation: Department of Advanced Aging Medicine, Chiba University Graduate School of Medicine, Chiba, Japan; Department of Orthopaedics, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Morikawa
authors.affiliation: Department of Orthopaedics, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Itoigawa
authors.affiliation: Department of Orthopaedics, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Nojiri
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sano
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Itoi
authors.affiliation: Department of Biomedical Imaging, Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Saijo
authors.affiliation: Department of Orthopaedics, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Department of Advanced Aging Medicine, Chiba University Graduate School of Medicine, Chiba, Japan. Electronic address: shimizut@chiba-u.jp.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D004548:Elasticity; D058430:Humeral Head / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D033401:Microscopy, Acoustic; D008859:Microscopy, Polarization; D018384:Oxidative Stress; D017006:Rotator Cuff / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D003094:Collagen; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Rotator cuff degeneration; Sod1; collagen fibers; enthesis; mechanical property; oxidative stress; scanning acoustic microscopy