title: Thinning of articular cartilage after joint unloading or immobilization. An experimental investigation of the pathogenesis in mice.
abstract: Moderate mechanical stress generated by normal joint loading and movement is essential for the maintenance of healthy articular cartilage. However, the effects of reduced loading caused by the absence of weight bearing or joint motion on articular cartilage and subchondral bone is still poorly understood. We aimed to characterize morphological and metabolic responses of articular cartilage and subchondral bone to decreased mechanical stress in vivo.
  
  
  
  Mice were subjected to periods of hindlimb unloading by tail suspension or external fixation of the knee joints. The articular surface was observed with digital microscope and the epiphyseal bone was assessed by micro-CT analysis. Articular cartilage and subchondral bone were further evaluated by histomorphometric, histochemical, and immunohistochemical analyses.
  
  
  
  The joint surface was intact, but thickness of both the total and uncalcified layer of articular cartilage were decreased both after joint unloading and immobilization. Subchondral bone atrophy with concomitant marrow expansion predisposed osteoclast activity at bone surface to invade into cartilaginous layer. Uncalcified cartilage showed decreased aggrecan content and increased aggrecanase expression. Alkaline phosphatase (ALP) activity was increased at uncalcified cartilage, whereas decreased at calcified cartilage. The distributions of hypertrophic chondrocyte markers remained unchanged.
  
  
  
  Thinning of articular cartilage induced by mechanical unloading may be mediated by metabolic changes in chondrocytes, including accelerated aggrecan catabolism and exquisitely modulated matrix mineralization, and cartilage matrix degradation and resorption by subchondral osteoclasts. Cartilage degeneration without chondrocyte hypertrophy under unloading condition indicate the possible existence of mechanism which is different from osteoarthritis pathogenesis.
authors.affiliation: Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Tomogaoka 7-10-2, Suma-ku, Kobe, 654-0142, Japan. Electronic address: cunorimousiraty@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Nomura
authors.affiliation: Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Tomogaoka 7-10-2, Suma-ku, Kobe, 654-0142, Japan. Electronic address: 7asdfghjklzxcvbnm@gmail.com.
authors.forename: N
authors.initials: N
authors.lastname: Sakitani
authors.affiliation: Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Tomogaoka 7-10-2, Suma-ku, Kobe, 654-0142, Japan; Department of Rehabilitation, St. Marianna University School of Medicine, Sugao 2-16-1, Miyamae-ku, Kawasaki, 216-8511, Japan. Electronic address: googrie588@gmail.com.
authors.forename: H
authors.initials: H
authors.lastname: Iwasawa
authors.affiliation: Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Tomogaoka 7-10-2, Suma-ku, Kobe, 654-0142, Japan. Electronic address: kohakoha1313@gmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Kohara
authors.affiliation: Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Tomogaoka 7-10-2, Suma-ku, Kobe, 654-0142, Japan. Electronic address: shoko.12.t@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Takano
authors.affiliation: Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Tomogaoka 7-10-2, Suma-ku, Kobe, 654-0142, Japan. Electronic address: wakio0820.kbu@gmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Wakimoto
authors.affiliation: School of Health Sciences, Graduate School of Medicine, Kyoto University, Kawahara-cho, Shogoin 53, Sakyo-ku, Kyoto-shi, Kyoto, 606-8507, Japan. Electronic address: kuroki.hiroshi.6s@kyoto-u.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Kuroki
authors.affiliation: Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Tomogaoka 7-10-2, Suma-ku, Kobe, 654-0142, Japan. Electronic address: morihide@harbor.kobe-u.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Moriyama
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D002358:Cartilage, Articular / Q000473:pathology* / Q000503:physiopathology; D019902:Chondrocytes / Q000648:ultrastructure; D004195:Disease Models, Animal; D007103:Immobilization; D007150:Immunohistochemistry; D007719:Knee Joint / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning / Q000379:methods; D010003:Osteoarthritis / Q000473:pathology / Q000503:physiopathology; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D013314:Stress, Mechanical
keywords: Aggrecan; Articular cartilage; Mechanical unloading; Mineralization; Osteoclast; Subchondral bone