title: Lectin-like, oxidized low-density lipoprotein receptor-1-deficient mice show resistance to age-related knee osteoarthritis.
abstract: The lectin-like, oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1)/ox-LDL system contributes to atherosclerosis and may be involved in cartilage degeneration. The purpose of this study was to determine whether the LOX-1/ox-LDL system contributes to age-related osteoarthritis (OA) in vivo, using LOX-1 knockout (LOX-1 KO) mice. Knee cartilage from 6, 12, and 18-month old (n = 10/group) C57Bl/6 wild-type (WT) and LOX-1 KO mice was evaluated by determining the Osteoarthritis Research Society International (OARSI) score of Safranin-O stained samples. The prevalence of knee OA in both mouse strains was also investigated. Expression levels of LOX-1, ox-LDL, runt-related transcription factor-2 (Runx2), type-X collagen (COL X), and matrix metalloproteinase-13 (MMP-13) in the articular chondrocytes were analyzed immunohistologically. No significant difference was observed in the mean scores of WT (2.00±0.61) and LOX-1 KO mice (2.00±0.49) at 6 months of age (P=1.00, n=10). At 12 and 18 months of age, the mean scores of LOX-1 KO mice (3.75±0.93 and 5.50±0.78) were significantly lower than those of WT mice (5.25±1.14 and 9.00±1.01; P&lt;0.001 in both cases; n=10). The prevalence of OA in LOX-1 KO mice was lower than that in WT mice at 12 and 18 months of age (40 vs 70%, 70 vs 90%, respectively; n=10). The expression levels of Runx2, COL X, and MMP-13 in articular chondrocytes significantly decreased in LOX-1 KO, mice compared with those in WT mice. The study indicated that the LOX-1/ox-LDL system in chondrocytes plays a role in the pathogenesis of age-related knee OA, which is potentially a target for preventing OA progression.
authors.affiliation: Kindai University Hospital. hazzhiko@med.kindai.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oda
authors.forename: Fumihisa
authors.initials: F
authors.lastname: Nakamura
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kakinoki
authors.forename: Masao
authors.initials: M
authors.lastname: Akagi
mesh_terms: D000375:Aging; D000818:Animals; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D024121:Collagen Type X / Q000096:biosynthesis / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D007719:Knee Joint / Q000378:metabolism* / Q000473:pathology; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051127:Scavenger Receptors, Class E / Q000096:biosynthesis / Q000172:deficiency*
chemical_list: D024121:Collagen Type X; D050659:Core Binding Factor Alpha 1 Subunit; C495138:Olr1 protein, mouse; C493716:Runx2 protein, mouse; D051127:Scavenger Receptors, Class E; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse