title: Chondroprotective effects of high-molecular-weight cross-linked hyaluronic acid in a rabbit knee osteoarthritis model.
abstract: OBJECTIVE
  We hypothesized that high-molecular-weight (MW) cross-linked (CL) hyaluronic acid (HA) improves joint lubrication and has an enhanced chondroprotective effect. We examined the histopathological changes and friction coefficients in osteoarthritic knee joints after injecting high-MW CL HA.
  
  
  METHODS
  A bilateral anterior cruciate ligament transection (ACLT) model in 20 Japanese white rabbits was used. From week 5 after transection, low-MW HA (0.8 × 10(6) Da; HA80) or high-MW CL HA (6 × 10(6) Da; HA600) was injected weekly into 10 right knee for 3 weeks; normal saline (NS) was injected into the 10 left knee. A sham operation was undertaken to exclude spontaneous osteoarthritis (OA) in five knees. Results were evaluated with macroscopy, histopathology (Kikuchi's score), biomechanical testing, and rheological assessment of the joint fluid viscoelasticity. Statistical analysis was performed using one-way analysis of variance with a 95% confidence interval (CI) (P < 0.05).
  
  
  RESULTS
  The macroscopic findings showed severely damaged cartilage in 30% of the NS group and 20% of the HA80 and HA600 groups and intact cartilage in 100% of the sham group. The histological scores and friction coefficients of the HA600 group were significantly lower than those of the NS group (P = 0.007 and P = 0.002, respectively). Viscoelasticity measurements of the joint fluid showed no significant differences between the three treatment groups.
  
  
  CONCLUSIONS
  High-MW CL HA exerts potential chondroprotective effects and produces superior friction coefficients. Our results suggest that HA600 delays the progression of OA effectively and improves joint lubrication significantly.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. Electronic address: selmorsy@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Elmorsy
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. Electronic address: tfunakoshi@gmail.com.
authors.forename: T
authors.initials: T
authors.lastname: Funakoshi
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. Electronic address: sasazawa230@gmail.com.
authors.forename: F
authors.initials: F
authors.lastname: Sasazawa
authors.affiliation: Division of Human Mechanical Systems and Design, Graduate School of Engineering, Hokkaido University, Sapporo, Japan. Electronic address: todoh@eng.hokudai.ac.jp.
authors.forename: M
authors.initials: M
authors.lastname: Todoh
authors.affiliation: Division of Human Mechanical Systems and Design, Graduate School of Engineering, Hokkaido University, Sapporo, Japan. Electronic address: tadano@eng.hokudai.ac.jp.
authors.forename: S
authors.initials: S
authors.lastname: Tadano
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. Electronic address: niwasaki@med.hokudai.ac.jp.
authors.forename: N
authors.initials: N
authors.lastname: Iwasaki
mesh_terms: D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries; D001169:Arthritis, Experimental / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002358:Cartilage, Articular / Q000473:pathology*; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004548:Elasticity; D005260:Female; D005269:Femur / Q000473:pathology; D017276:Friction; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D007270:Injections, Intra-Articular; D008153:Lubrication / Q000379:methods; D008970:Molecular Weight; D020370:Osteoarthritis, Knee / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D011817:Rabbits; D013582:Synovial Fluid / Q000502:physiology; D014783:Viscosity; D055676:Viscosupplementation / Q000379:methods; D055675:Viscosupplements / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D055675:Viscosupplements; D006820:Hyaluronic Acid
keywords: Hyaluronic acid; Molecular weight; Osteoarthritis; Viscoelasticity