title: Enhanced levels of non-enzymatic glycation and pentosidine crosslinking in spontaneous osteoarthritis progression.
abstract: OBJECTIVE
  To test the hypothesis that heightened advanced glycation endproducts (AGEs) content in cartilage accelerates the progression of spontaneous osteoarthritis (OA) in the Hartley guinea pig (HGP) model.
  
  
  METHODS
  Twenty-eight male, 3-month-old HGPs were used. Eight were left untreated as a baseline control group and sacrificed at 3 months of age (n = 4) and 9 months of age (n = 4; age-matched controls). The other 20 HGPs received intra-articular knee injections in the right knee whereas the left knees acted as contra-lateral non-injected controls. Injections consisted of 100 μl phosphate buffered saline (PBS; n = 10) or PBS+2.0 M D-(-)-Ribose (n = 10). Injections were given once weekly for 24 weeks. At the end of the treatment period, the tibiae were fixed with formalin, scanned with microCT for sub-chondral bone mineral density, and then histological slides were prepared, stained with Safranin-O with Fast Green counter stain and scored using the OARSI-HISTOgp scheme. Cartilage pentosidine (established biomarker for AGEs) content, collagen content (% dry mass), glucosaminoglycan GAG-to-collagen ratio (μg/μg), GAG-to-DNA ratio and DNA-to-collagen ratio were measured.
  
  
  RESULTS
  Pentosidine content increased greatly due to PBS + Ribose injection (P < 0.0001) and reached levels found in cartilage from 80-year-old humans. Surprisingly, mean OARSI-HISTOgp scores for both the injected and contra-lateral controls in the PBS + Ribose group were not detectably different, nor were they different from the mean score for the age-matched control group.
  
  
  CONCLUSIONS
  AGEs accumulation due to intra-articular ribose-containing injections in the HGP model of spontaneous knee OA did not enhance disease progression.
authors.affiliation: Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Ontario, Canada. willett@lunenfeld.ca
authors.forename: T L
authors.initials: TL
authors.lastname: Willett
authors.forename: R
authors.initials: R
authors.lastname: Kandel
authors.forename: J N A
authors.initials: JN
authors.lastname: De Croos
authors.forename: N C
authors.initials: NC
authors.lastname: Avery
authors.forename: M D
authors.initials: MD
authors.lastname: Grynpas
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006168:Guinea Pigs; D007270:Injections, Intra-Articular; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D010003:Osteoarthritis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012266:Ribose / Q000008:administration & dosage; D055114:X-Ray Microtomography
chemical_list: D017127:Glycation End Products, Advanced; D012266:Ribose; D003094:Collagen; D001120:Arginine; C062187:pentosidine; D008239:Lysine