title: In vitro glycation of articular cartilage alters the biomechanical response of chondrocytes in a depth-dependent manner.
abstract: OBJECTIVE
  To determine if increasing cartilage cross-links through in vitro glycation of cartilage explants can alter the biomechanical response of chondrocytes to compressive deformation.
  
  
  METHODS
  Bovine osteochondral explants were either incubated with cell culture solution supplemented with (n = 7) or without (n = 7) ribose for 42 h in order to induce glycation. Deformation-induced changes in cell volume, dimensions and local tissue strains were determined through confocal laser scanning microscopy (CLSM) and the use of a custom built micro-compression device. Osteochondral explants were also utilized to demonstrate changes in depth-wise tissue properties, biomechanical tissue properties and cross-links such as pentosidine (Pent), hydroxylysyl pyridinoline (HP) and lysyl pyridinoline (LP).
  
  
  RESULTS
  The ribose treated osteochondral samples experienced reduced cell volume deformation in the upper tissue zone by ∼ 8% (P = 0.005), as compared the control samples, through restricting cell expansion. In the deeper tissue zone, cell volume deformation was increased by ∼ 12% (P < 0.001) via the transmission of mechanical signals further into the tissue depth. Biomechanical testing of the ribose treated osteochondral samples demonstrated an increase in the equilibrium and dynamic strain dependent moduli (P < 0.001 and P = 0.008, respectively). The biochemical analysis revealed an increase in Pent cross-links (P < 0.001). Depth-wise tissue property analyses revealed increased levels of carbohydrate content, greater levels of fixed charge density and an increased carbohydrate to protein ratio from 6 to 16%, 55-100% and 72-79% of the normalized tissue thickness (from the surface), respectively, in the ribose-treated group (P < 0.05).
  
  
  CONCLUSIONS
  In vitro glycation alters the biomechanical response of chondrocytes in cartilage differently in upper and deeper zones, offering possible insights into how aging could alter cell deformation behavior in cartilage.
authors.affiliation: Department of Applied Physics, University of Eastern Finland, Kuopio FI-70211, Finland. Electronic address: jfickbiomaterials@yahoo.com.
authors.forename: J M
authors.initials: JM
authors.lastname: Fick
authors.affiliation: Department of Applied Physics, University of Eastern Finland, Kuopio FI-70211, Finland.
authors.forename: M R J
authors.initials: MR
authors.lastname: Huttu
authors.affiliation: Department of Applied Physics, University of Eastern Finland, Kuopio FI-70211, Finland.
authors.forename: M J
authors.initials: MJ
authors.lastname: Lammi
authors.affiliation: Department of Applied Physics, University of Eastern Finland, Kuopio FI-70211, Finland.
authors.forename: R K
authors.initials: RK
authors.lastname: Korhonen
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects / Q000502:physiology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002417:Cattle; D048429:Cell Size / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006031:Glycosylation; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D012266:Ribose / Q000378:metabolism / Q000494:pharmacology*; D013314:Stress, Mechanical
chemical_list: D012266:Ribose
keywords: Aging; Articular cartilage; Chondrocyte deformation; Cross-linking; Ribose