title: Destabilization of the medial meniscus leads to subchondral bone defects and site-specific cartilage degeneration in an experimental rat model.
abstract: OBJECTIVE
  This study aimed to investigate subchondral bone changes using micro-computed tomography (micro-CT) and regional differences in articular cartilage degeneration, focusing on changes of cartilage covered by menisci, in the early phase using a destabilization of the medial meniscus (DMM) model.
  
  
  METHODS
  The DMM model was created as an experimental rat osteoarthritis (OA) model (12 weeks old; n = 24). At 1, 2, and 4 weeks after surgery, the rats were sacrificed, and knee joints were scanned using a Micro-CT system. Histological sections of the medial tibial plateau, which was divided into inner, middle, and outer regions, were prepared and scored using the modified OARSI scoring system. The cartilage thickness was also calculated, and matrix metalloproteinase 13 (MMP13), Col2-3/4c, and vascular endothelial growth factor (VEGF) expression was assessed immunohistochemically.
  
  
  RESULTS
  Subchondral bone defects were observed in the middle region, in which the cartilage thickness decreased over time after surgery, and these defects were filled with MMP13- and VEGF-expressing fibrous tissue. The OARSI score increased over time in the middle region, and the score was significantly higher in the middle region than in the inner and outer regions at 1, 2, and 4 weeks after surgery. Col2-3/4c and MMP13 expression was observed primarily in the meniscus-covered outer region, in which the cartilage thickness increased over time.
  
  
  CONCLUSIONS
  Loss of meniscal function caused cartilage degeneration and subchondral bone defects in the early phase site-specifically in the middle region. Furthermore, our results might indicate cartilage covered by menisci is easily degraded resulting in osmotic swelling of the cartilage in early OA.
authors.affiliation: Department of Motor Function Analysis, Human Health Sciences, Graduate School of Medicine, Kyoto University, Japan. Electronic address: iijima.hirotaka.75s@st.kyoto-u.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Iijima
authors.affiliation: Department of Development and Rehabilitation of Motor Function, Human Health Sciences, Graduate School of Medicine, Kyoto University, Japan. Electronic address: aoyama.tomoki.4e@kyoto-u.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Aoyama
authors.affiliation: Department of Motor Function Analysis, Human Health Sciences, Graduate School of Medicine, Kyoto University, Japan. Electronic address: ito.akira.27n@st.kyoto-u.ac.jp.
authors.forename: A
authors.initials: A
authors.lastname: Ito
authors.affiliation: Department of Motor Function Analysis, Human Health Sciences, Graduate School of Medicine, Kyoto University, Japan. Electronic address: tajino.junichi.57z@st.kyoto-u.ac.jp.
authors.forename: J
authors.initials: J
authors.lastname: Tajino
authors.affiliation: Department of Motor Function Analysis, Human Health Sciences, Graduate School of Medicine, Kyoto University, Japan. Electronic address: nagai.momoko.36v@st.kyoto-u.ac.jp.
authors.forename: M
authors.initials: M
authors.lastname: Nagai
authors.affiliation: Department of Motor Function Analysis, Human Health Sciences, Graduate School of Medicine, Kyoto University, Japan. Electronic address: zhang.xiangkai.48v@st.kyoto-u.ac.jp.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Motor Function Analysis, Human Health Sciences, Graduate School of Medicine, Kyoto University, Japan. Electronic address: yamaguchi.shouki.26n@st.kyoto-u.ac.jp.
authors.forename: S
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Gifu University, Japan. Electronic address: hakiyama@kuhp.kyoto-u.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: Department of Motor Function Analysis, Human Health Sciences, Graduate School of Medicine, Kyoto University, Japan. Electronic address: kuroki.hiroshi.6s@kyoto-u.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Kuroki
mesh_terms: D000818:Animals; D019902:Chondrocytes / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D024043:Collagen Type II / Q000378:metabolism; D024061:Collagen Type III; D024141:Collagen Type IV; D017364:Collagenases / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008592:Menisci, Tibial / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D010003:Osteoarthritis / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D024043:Collagen Type II; D024061:Collagen Type III; D024141:Collagen Type IV; D042461:Vascular Endothelial Growth Factor A; D017364:Collagenases; D053509:Matrix Metalloproteinase 13
keywords: Cartilage covered by menisci; Cartilage degeneration; Destabilization of medial meniscus; Subchondral bone defects