title: Topographical analysis of the structural, biochemical and dynamic biomechanical properties of cartilage in an ovine model of osteoarthritis.
abstract: OBJECTIVE
  The relationship between the topographical variations in the structural, biochemical and dynamic biomechanical properties of articular cartilage (AC) before and 6 months after meniscectomy has not been previously reported but is clearly relevant to our understanding of the role of mechanical factors on the pathogenesis of osteoarthritis (OA). The objective of this study was to address this deficiency using an ovine model of OA induced by bilateral lateral meniscectomy.
  
  
  METHODS
  The dynamic effective shear modulus (G*) and phase lag were determined ex vivo at 26 individual locations over the medial and lateral tibial plateaux of non-operated and meniscectomized ovine joints 6 months after surgery using a novel hand-held dynamic indentation probe. AC thickness was measured with a needle penetration probe. The AC from the same topographical locations as indented was then analysed for sulfated glycosaminoglycans (S-GAG) as a measure of proteoglycan (PG) levels, collagen and water content. Histological evaluation of the collagen organization using quantitative analysis of birefringence intensity was performed on stained tissue sections from the same topographical locations of each animal.
  
  
  RESULTS
  It was demonstrated that the AC of the entire lateral tibial compartment of the meniscectomized joints underwent significant local degenerative and compensatory changes as indicated by a decreased G* and an increase in phase lag and water content. This was accompanied by a decrease in PG content of the AC of the middle and inner regions. While the AC of the outer region of the lateral meniscectomized compartment showed a marked increase in PG content and a more than two-fold increase in thickness, these tissues were also found to be structurally inferior, as indicated by a decreased G* and abnormal collagen birefringence intensity. The AC thickness was elevated at all locations of the lateral and medial tibial plateau of the meniscectomized joints. Strong and significant correlations between the biomechanical and biochemical data were established for a number of the parameters examined, especially between collagen content and G*, collagen content and AC thickness, and G* and AC thickness. An inverse correlation between S-GAG content and G* was only apparent in non-operated control tissues, whereas correlations between collagen and water content, water content and G*, and water content and thickness were evident for AC of the meniscectomized tibial plateaux. Less striking changes were noted in the medial compartment where the intact meniscus remained in place. However, elevated PG content, thicker AC together with slight changes in G* suggested an early hypertrophic response in these tissues.
  
  
  CONCLUSIONS
  This study has highlighted the variable response of AC in different topographical regions of meniscectomized joints to the altered mechanical stresses introduced by this surgical procedure. The AC at the joint margins, while thicker and richer in PG, was found to be biomechanically softer (lower shear modulus) than normal AC, and because of this, would be expected to undergo degenerative changes with time leading to the onset of OA.
authors.affiliation: Orthopaedic Research Institute, St George Hospital Campus (University of New South Wales), Kogarah, NSW, Australia.
authors.forename: R C
authors.initials: RC
authors.lastname: Appleyard
authors.forename: D
authors.initials: D
authors.lastname: Burkhardt
authors.forename: P
authors.initials: P
authors.lastname: Ghosh
authors.forename: R
authors.initials: R
authors.lastname: Read
authors.forename: M
authors.initials: M
authors.lastname: Cake
authors.forename: M V
authors.initials: MV
authors.lastname: Swain
authors.forename: G A C
authors.initials: GA
authors.lastname: Murrell
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000737:chemistry*; D003094:Collagen / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006614:Hindlimb; D008592:Menisci, Tibial; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000503:physiopathology*; D011509:Proteoglycans / Q000378:metabolism*; D012756:Sheep
chemical_list: D006025:Glycosaminoglycans; D011509:Proteoglycans; D003094:Collagen