title: Lectin-like oxidized low density lipoprotein receptor 1-deficient mice show resistance to instability-induced osteoarthritis.
abstract: OBJECTIVE
  The lectin-like oxidized low density lipoprotein (ox-LDL) receptor 1 (LOX-1)/ox-LDL system, which contributes to the pathogenesis of atherosclerosis, may be involved in the development of osteoarthritis (OA). However, the mechanisms by which the LOX-1/ox-LDL system contributes to OA development in vivo are unclear. In this study, we investigated the direct involvement of LOX-1/ox-LDL in OA development by using LOX-1-knockout (LOX-1(-)/(-)) mice in a joint instability-induced model of OA.
  
  
  METHODS
  OA development was evaluated with histological scoring at 4 and 8 weeks after surgery to induce knee destabilization in LOX-1(+)/(+) and LOX-1(-)/(-) mice. Immunohistological analysis was used to evaluate the expression of LOX-1, ox-LDL, Runt-related transcription factor 2 (Runx2), and type X collagen (COL X) in articular chondrocytes and osteophyte-forming cells. In addition, double immunofluorescence staining was performed to determine the relationships between LOX-1 and Runx2 or COL X expression.
  
  
  RESULTS
  In the model of knee destabilization, symptoms were significantly suppressed in LOX-1(-)/(-) mice. LOX-1, ox-LDL, Runx2, and COL X were overexpressed in articular chondrocytes and osteophyte-forming cells in LOX-1(+)/(+) mice and were significantly downregulated in articular chondrocytes and osteophyte-forming cells in LOX-1(-)/(-) mice compared with those in LOX-1(+)/(+) mice. Double immunostaining indicated that LOX-1 localization coincided with Runx2 and COL X expression.
  
  
  CONCLUSIONS
  These data indicate that the LOX-1/ox-LDL system plays a pivotal role in the pathogenesis of instability-induced OA through endochondral ossification. LOX-1-positive chondrocytes and osteophyte-forming cells may be possible targets to prevent disease progression in OA.
authors.affiliation: a Department of Orthopaedic Surgery , Kindai University Faculty of Medicine , Osaka , Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: a Department of Orthopaedic Surgery , Kindai University Faculty of Medicine , Osaka , Japan.
authors.forename: S
authors.initials: S
authors.lastname: Mori
authors.affiliation: a Department of Orthopaedic Surgery , Kindai University Faculty of Medicine , Osaka , Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Oda
authors.affiliation: b Department of Bioscience , National Cardiovascular Centre Research Institute , Osaka , Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nakano
authors.affiliation: c Department of Physiology , Shinshu University School of Medicine , Nagano , Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sawamura
authors.affiliation: a Department of Orthopaedic Surgery , Kindai University Faculty of Medicine , Osaka , Japan.
authors.forename: M
authors.initials: M
authors.lastname: Akagi
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental; D019902:Chondrocytes / Q000378:metabolism; D024121:Collagen Type X / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D007593:Joint Instability; D007719:Knee Joint; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008592:Menisci, Tibial / Q000601:surgery; D051379:Mice; D018345:Mice, Knockout; D020370:Osteoarthritis, Knee / Q000235:genetics* / Q000378:metabolism; D054850:Osteophyte; D051127:Scavenger Receptors, Class E / Q000235:genetics* / Q000378:metabolism; D000070600:Tibial Meniscus Injuries
chemical_list: D024121:Collagen Type X; D050659:Core Binding Factor Alpha 1 Subunit; D008077:Lipoproteins, LDL; C495138:Olr1 protein, mouse; C493716:Runx2 protein, mouse; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein