title: Exercise intervention increases expression of bone morphogenetic proteins and prevents the progression of cartilage-subchondral bone lesions in a post-traumatic rat knee model.
abstract: This study aimed to determine whether treadmill walking (TW) prevents the progression of post-traumatic osteoarthritic changes in cartilage-subchondral bone unit, and whether the exercise timing changes the exercise efficacy in destabilized medial meniscus (DMM) rat knees.
  
  
  
  Twelve-week-old male Wistar rats underwent DMM surgery on their right knees and sham surgery on their left knees and were assigned to either the sedentary (n = 10) or walking (n = 24) groups. The rats in the walking group were subjected to TW from day 2 through 4 weeks, from 4 through 8 weeks, or from day 2 through 8 weeks (n = 8 per group). Osteoarthritic changes of cartilage and subchondral bone were assessed with micro-computed tomography, histology, and immunohistochemistry 8 weeks after surgery.
  
  
  
  TW prevented the progression of cartilage and subchondral bone lesions induced by the DMM, and increased bone morphogenetic protein (BMP)-2 and -6 expressions in superficial zone chondrocytes and bone-lining cells including osteoblasts. Furthermore, the TW-induced increase in BMPs varied with the exercise timing. Beginning TW 4 weeks after DMM surgery was the best option for increasing BMPs, coinciding with the most robust prevention of osteoarthritic changes.
  
  
  
  TW increased the expression of BMPs and prevented the progression of cartilage-subchondral bone lesions in rat knees with a DMM. Selective exercise timing may be a key factor in the development of an exercise regimen for preventing the progression of post-traumatic osteoarthritis (PTOA). Furthermore, exercise may have favorable effects even after the PTOA has been developed.
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: 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: 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: 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: 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. 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: 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: kuroki.hiroshi.6s@kyoto-u.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Kuroki
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins; D002358:Cartilage, Articular; D005081:Exercise Therapy; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D055114:X-Ray Microtomography
chemical_list: D019485:Bone Morphogenetic Proteins
keywords: Bone micro-CT; Bone morphogenetic protein; Cartilage; Exercise; Osteoarthritis