title: Subchondral plate porosity colocalizes with the point of mechanical load during ambulation in a rat knee model of post-traumatic osteoarthritis.
abstract: OBJECTIVE
  This study investigated the association between spatiotemporal cartilage-subchondral bone plate alterations and mechanical load during ambulation in an experimental rat model of destabilized medial meniscus (DMM).
  
  
  METHODS
  Twelve-week-old Wistar rats (n = 38) underwent DMM surgery on the right knee and sham surgery on the left knee. At 2 and 4 weeks after surgery, subchondral bone changes were evaluated via micro-computed tomography with various knee flexion angles to simulate weight-bearing during rat ambulation under a 3-dimensional motion capture apparatus. Additionally, the biomechanical properties, histology, and ultrastructure of the medial tibia and femoral condyle were evaluated.
  
  
  RESULTS
  Focal subchondral bone plate perforations were confirmed in the medial tibia within 2 weeks after surgery and were aggravated rapidly 2 weeks later. This subchondral plate porosity colocalized with articular cartilage lesions as confirmed by histology and scanning electron microscopy, and coincided with the likely point of contact between the posterior femoral condyle and tibial plateau during ambulation. Biomechanical properties were confirmed at the medial tibia, at which stiffness was reduced to approximately half that of the sham-operated knee at 4 weeks after surgery.
  
  
  CONCLUSIONS
  Cartilage-subchondral bone plate alterations localized in the region of the point of mechanical load during ambulation in DMM-operated knees, at which the mechanical integrity of cartilage was impaired. These results indicate that DMM-induced increases in mechanical load play an important role in the pathogenesis of early post-traumatic osteoarthritis (OA), and it might accelerate the development of the disease via cartilage-subchondral bone plate crosstalk through increased subchondral plate perforations.
authors.affiliation: Department of Motor Function Analysis, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Japan Society for the Promotion of Science, Tokyo, 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, Kyoto, 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, Kyoto, Japan. Electronic address: junichi_tajino@icloud.com.
authors.forename: J
authors.initials: J
authors.lastname: Tajino
authors.affiliation: Japan Society for the Promotion of Science, Tokyo, Japan; Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: legacy-tsr.akira_itoh@live.jp.
authors.forename: A
authors.initials: A
authors.lastname: Ito
authors.affiliation: Congenital Anomaly Research Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: nagai@cac.med.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, Kyoto, Japan; Japan Society for the Promotion of Science, Tokyo, Japan. Electronic address: yamaguchi.shouki.26n@st.kyoto-u.ac.jp.
authors.forename: S
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of Motor Function Analysis, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, 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, Kyoto, Japan. Electronic address: kiyan.wataru.32c@st.kyoto-u.ac.jp.
authors.forename: W
authors.initials: W
authors.lastname: Kiyan
authors.affiliation: Department of Motor Function Analysis, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: kuroki.hiroshi.6s@kyoto-u.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Kuroki
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007718:Knee Injuries / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology; D008297:Male; D008855:Microscopy, Electron, Scanning; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology; D016062:Porosity; D051381:Rats; D017208:Rats, Wistar; D000070600:Tibial Meniscus Injuries; D016138:Walking; D016474:Weight-Bearing; D055114:X-Ray Microtomography
chemical_list: D003094:Collagen
keywords: Bone μCT; Cross-talk; Mechanical load; Osteoarthritis; Subchondral plate perforation