title: Comparison of mouse and human ankles and establishment of mouse ankle osteoarthritis models by surgically-induced instability.
abstract: Prevalence of ankle osteoarthritis (OA) is lower than that of knee OA, however, the molecular mechanisms underlying the difference remain unrevealed. In the present study, we developed mouse ankle OA models for use as tools to investigate pathophysiology of ankle OA and molecular characteristics of ankle cartilage.
  
  
  
  We anatomically and histologically examined ankle and knee joints of C57BL/6 mice, and compared them with human samples. We examined joints of 8-week-old and 25-month-old mice. For experimental models, we developed three different ankle OA models: a medial model, a lateral model, and a bilateral model, by resection of respective structures. OA severity was evaluated 8 weeks after the surgery by safranin O staining, and cartilage degradation in the medial model was sequentially examined.
  
  
  
  Anatomical and histological features of human and mouse ankle joints were comparable. Additionally, the mouse ankle joint was more resistant to cartilage degeneration with aging than the mouse knee joint. In the medial model, the tibiotalar joint was markedly affected while the subtalar joint was less degenerated. In the lateral model, the subtalar joint was mainly affected while the tibiotalar joint was less altered. In the bilateral model, both joints were markedly degenerated. In the time course of the medial model, TdT-mediated dUTP nick end labeling (TUNEL) staining and Adamts5 expression were enhanced at early and middle stages, while Mmp13 expression was gradually increased during the OA development.
  
  
  
  Since human and mouse ankles are comparable, the present models will contribute to ankle OA pathophysiology and general cartilage research in future.
authors.affiliation: Sensory & Motor System Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: s5chang@yahoo.co.jp.
authors.forename: Song Ho
authors.initials: SH
authors.lastname: Chang
authors.affiliation: Sensory & Motor System Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: yasui.tokyo@gmail.com.
authors.forename: T
authors.initials: T
authors.lastname: Yasui
authors.affiliation: Sensory & Motor System Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: TAKETOMIS-ORT@h.u-tokyo.ac.jp.
authors.forename: S
authors.initials: S
authors.lastname: Taketomi
authors.affiliation: Sensory & Motor System Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: matumot-tky@umin.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. Electronic address: shuri@pharm.showa-u.ac.jp.
authors.forename: J R
authors.initials: JR
authors.lastname: Kim-Kaneyama
authors.affiliation: Sensory & Motor System Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: oomiya9ort@yahoo.co.jp.
authors.forename: T
authors.initials: T
authors.lastname: Omiya
authors.affiliation: Sensory & Motor System Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: hosakayort@gmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Hosaka
authors.affiliation: Sensory & Motor System Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: hiroshi_inu0707@yahoo.co.jp.
authors.forename: H
authors.initials: H
authors.lastname: Inui
authors.affiliation: Sensory & Motor System Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: grandbleu_1024@yahoo.co.jp.
authors.forename: Y
authors.initials: Y
authors.lastname: Omata
authors.affiliation: Sensory & Motor System Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: yamagami-tky@umin.ac.jp.
authors.forename: R
authors.initials: R
authors.lastname: Yamagami
authors.affiliation: Bone and Cartilage Regenerative Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: Mori.Daisuke@technopro.com.
authors.forename: D
authors.initials: D
authors.lastname: Mori
authors.affiliation: Bone and Cartilage Regenerative Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: fumikoyano706@gmail.com.
authors.forename: F
authors.initials: F
authors.lastname: Yano
authors.affiliation: Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: uichung-tky@umin.ac.jp.
authors.forename: U
authors.initials: U
authors.lastname: Chung
authors.affiliation: Sensory & Motor System Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: tanakas-ort@h.u-tokyo.ac.jp.
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Sensory & Motor System Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Bone and Cartilage Regenerative Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: tasaitou-tky@umin.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Saito
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D000843:Ankle Joint / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007593:Joint Instability / Q000150:complications*; D007719:Knee Joint / Q000033:anatomy & histology / Q000473:pathology; D008023:Ligaments, Articular / Q000601:surgery; D008297:Male; D008810:Mice, Inbred C57BL; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D013045:Species Specificity; D013710:Tendons / Q000601:surgery; D055114:X-Ray Microtomography / Q000379:methods
keywords: Animal model; Ankle; Chondrocytes; Osteoarthritis