title: Therapeutic effects of intra-articular ultra-purified low endotoxin alginate administration on an experimental canine osteoarthritis model.
abstract: OBJECTIVE
  This study aimed to elucidate the therapeutic effects of intra-articular administration of ultra-purified low endotoxin alginate (UPLE-alginate) on osteoarthritis (OA) using a canine anterior cruciate ligament transection (ACLT) model.
  
  
  METHODS
  We used 20 beagle dogs. ACLT was performed on the left knee of each dog and a sham operation was performed on the right knee as a control. All animals were randomly divided into the control (saline) and therapeutic (UPLE-alginate) groups. Animals in the control and therapeutic groups received weekly injections with 0.7 mL normal saline or 0.7 mL 0.5% UPLE-alginate, respectively, from 0 to 3 weeks after ACLT or sham operation. At 9 weeks after ACLT, the knee joints of all animals were observed using arthroscopy. All animals were euthanized at 14 weeks after ACLT and evaluated using morphologic assessment, histologic assessment, and biomechanical testing.
  
  
  RESULTS
  Arthroscopic findings showed intact cartilage surface in both groups. Morphologic findings in the therapeutic group showed milder degeneration compared with those of the control group, but there were no significant differences between groups. Histologic scores of the medial femoral condyle (MFC) and lateral femoral condyle (LFC) were better in the therapeutic group than the control group (MFC: p = 0.009, LFC: p = 0.009). Joint lubrication did not differ significantly between groups.
  
  
  CONCLUSIONS
  Intra-articular administration of UPLE-alginate in the early stage of OA slowed disease progression in canines. UPLE-alginate may have potential as a therapeutic agent for OA patients and reduce the number of patients who need to undergo total joint arthroplasty.
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Tsukuda
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Onodera
authors.affiliation: Department of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Izumisawa
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kasahara
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Igarashi
authors.affiliation: Business Development Division, Mochida Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ohzawa
authors.affiliation: Division of Human Mechanical Systems and Design, Faculty of Engineering, Hokkaido University, Sapporo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Todoh
authors.affiliation: Division of Human Mechanical Systems and Design, Faculty of Engineering, Hokkaido University, Sapporo, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tadano
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Iwasaki
mesh_terms: D000464:Alginates / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000000981:diagnostic imaging / Q000601:surgery; D001182:Arthroscopy; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D004731:Endotoxins / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D005269:Femur / Q000187:drug effects / Q000601:surgery; D017276:Friction; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007270:Injections, Intra-Articular; D007596:Joints / Q000187:drug effects; D008153:Lubrication; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D011859:Radiography
chemical_list: D000464:Alginates; D004731:Endotoxins; D006603:Hexuronic Acids; D020723:Glucuronic Acid
keywords: UPLE-alginate; canine OA model; cartilage; intra-articular injection; osteoarthritis