title: Preventing effects of joint contracture by high molecular weight hyaluronan injections in a rat immobilized knee model.
abstract: OBJECTIVE
  To elucidate preventive effects of high molecular weight hyaluronan (HMWHA) on the joint capsule of immobilized knees in rats.
  
  
  METHODS
  Unilateral knee joints of rats were immobilized with an internal fixator. Either 50 μl of HMWHA (Im-HA group) or 50 μl of saline (control group) was administered intra-articularly once a week after surgery. Sagittal sections were prepared from the medial midcondylar region of the knee joints and assessed by histological, histomorphometric, and immunohistochemical methods. Gene expressions related to inflammation, fibrotic conditions, and hypoxia were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Tissue elasticity of the capsule from both groups was examined using a scanning acoustic microscope (SAM).
  
  
  RESULTS
  CD68 positive cells decreased in adhesion areas of the synovial membrane after 1 week in both groups. The length of the superficial layer in the synovial membrane of the Im-HA group was significantly longer than those in the control group over a period of 4 to 8 weeks with significantly small numbers of CD68 positive cells. The gene expressions of IL-6, IL-1β, TGF-β, CTGF, COL1a1, COL3a1, SPARC, and HIF1-α were significantly lower in the Im-HA group compared to those in the control group. The sound speed of the anterior and posterior synovial membrane increased significantly (a reduction in elasticity) in the control group compared to those in the Im-HA group during weeks 1 to 4.
  
  
  CONCLUSIONS
  This study demonstrated that HMWHA injections suppressed inflammatory, fibrotic, and hypoxic conditions observed in the immobilized joint capsule.
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University School of Medicine 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kanazawa
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University School of Medicine 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hagiwara
authors.affiliation: Divisions of Aging and Geriatric Dentistry, Tohoku University Graduate School of Dentistry 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuchiya
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University School of Medicine 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yabe
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University School of Medicine 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Sonofuchi
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University School of Medicine 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Koide
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University School of Medicine 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Sekiguchi
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University School of Medicine 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Itaya
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University School of Medicine 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ando
authors.affiliation: Department of Biomedical Imaging, Tohoku University Graduate School of Biomedical Engineering 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Saijo
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University School of Medicine 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Itoi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003286:Contracture / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D000860:Hypoxia / Q000150:complications / Q000517:prevention & control; D007103:Immobilization; D007249:Inflammation / Q000150:complications / Q000517:prevention & control; D007267:Injections; D017746:Joint Capsule / Q000187:drug effects* / Q000473:pathology; D007719:Knee Joint / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology; D000267:Tissue Adhesions
chemical_list: D015415:Biomarkers; D006820:Hyaluronic Acid
keywords: Joint immobilization; fibrosis; high molecular weight hyaluronan; hypoxia; inflammation; joint contracture