title: Depth-wise progression of osteoarthritis in human articular cartilage: investigation of composition, structure and biomechanics.
abstract: OBJECTIVE
  Osteoarthritis (OA) is characterized by the changes in structure and composition of articular cartilage. However, it is not fully known, what is the depth-wise change in two major components of the cartilage solid matrix, i.e., collagen and proteoglycans (PGs), during OA progression. Further, it is unknown how the depth-wise changes affect local tissue strains during compression. Our aim was to address these issues.
  
  
  METHODS
  Data from the previous microscopic and biochemical measurements of the collagen content, distribution and orientation, PG content and distribution, water content and histological grade of normal and degenerated human patellar articular cartilage (n=73) were reanalyzed in a depth-wise manner. Using this information, a composition-based finite element (FE) model was used to estimate tissue function solely based on its composition and structure.
  
  
  RESULTS
  The orientation angle of collagen fibrils in the superficial zone of cartilage was significantly less parallel to the surface (P<0.05) in samples with early degeneration than in healthy samples. Similarly, PG content was reduced in the superficial zone in early OA (P<0.05). However, collagen content decreased significantly only at the advanced stage of OA (P<0.05). The composition-based FE model showed that under a constant stress, local tissue strains increased as OA progressed.
  
  
  CONCLUSIONS
  For the first time, depth-wise point-by-point statistical comparisons of structure and composition of human articular cartilage were conducted. The present results indicated that early OA is primarily characterized by the changes in collagen orientation and PG content in the superficial zone, while collagen content does not change until OA has progressed to its late stage. Our simulation results suggest that impact loads in OA joint could create a risk for tissue failure and cell death.
authors.affiliation: Department of Physics, University of Kuopio, Kuopio, Finland. simo.saarakkala@uku.fi
authors.forename: S
authors.initials: S
authors.lastname: Saarakkala
authors.forename: P
authors.initials: P
authors.lastname: Julkunen
authors.forename: P
authors.initials: P
authors.lastname: Kiviranta
authors.forename: J
authors.initials: J
authors.lastname: Mäkitalo
authors.forename: J S
authors.initials: JS
authors.lastname: Jurvelin
authors.forename: R K
authors.initials: RK
authors.lastname: Korhonen
mesh_terms: D000328:Adult; D002102:Cadaver; D002358:Cartilage, Articular / Q000378:metabolism* / Q000503:physiopathology*; D003094:Collagen / Q000032:analysis* / Q000648:ultrastructure; D020342:Finite Element Analysis; D005583:Fourier Analysis; D006801:Humans; D008859:Microscopy, Polarization; D008875:Middle Aged; D008954:Models, Biological; D020370:Osteoarthritis, Knee / Q000145:classification / Q000378:metabolism* / Q000503:physiopathology*; D011509:Proteoglycans / Q000032:analysis* / Q000648:ultrastructure; D013314:Stress, Mechanical
chemical_list: D011509:Proteoglycans; D003094:Collagen