Biomechanical, histologic and macroscopic assessment of articular cartilage in a sheep model of osteoarthritis.
OBJECTIVE
Our primary objective was to explore the full potential of the ovine medial meniscectomy (MMx) model of early osteoarthritis (OA) for studies to validate non-destructive articular cartilage (AC) assessments and therapeutic interventions. Our secondary objective was to re-evaluate the relationships between the different types of AC assessment after MMx in sheep.


METHODS
Macroscopic assessments, dynamic shear modulus (G*), phase lag and AC thickness measurements were performed at a total of 5437 reference points on all six articular surfaces in four normal joints and 16 MMx ovine stifle (knee) joints. Comparisons with histologic assessments of gross structural damage, collagen organisation (birefringence) and proteoglycan content were possible at 702 of these points.


RESULTS
Histologic gross structural damage and proteoglycan loss were seen throughout the joint with greatest severity (fibrillation) in closest proximity to the MMx site. Increases in AC (30-50%) thickness, reductions in G* (30-40%) and collagen birefringence intensity (15-30%) occurred more evenly throughout the joint. Macroscopic softening was evident only when G* declined by 80%. G* correlated with AC thickness (rho=-0.47), collagen organisation rho=0.44), gross structural damage (rho=-0.44) and proteoglycan content (rho=0.42). Multivariate analysis showed that collagen organisation contributed twice as much to dynamic shear modulus (t=6.66 as proteoglycan content (t=3.21). Collagen organisation (rho=0.11) and proteoglycan content (rho=0.09) correlated only weakly to phase lag.


CONCLUSIONS
Macroscopic assessments were insensitive to AC softening suggesting that arthroscopic assessments of AC status might also perform poorly. Collagen integrity was more important for the maintenance of AC stiffness (G*) than proteoglycan content. The development of major AC softening and thickening throughout the joint following MMx suggested involvement of non-mechanical (e.g., protein and biochemical) chemical and cytokine mediated processes in addition to the disturbance in biomechanical loading. The ovine MMx model provides a setting in which the spectrum of AC changes associated with the initiation and progression of OA may be evaluated.
Oakley
S P
SP
Department of Rheumatology, St. George Hospital, University of New South Wales, Gray St., Kogarah, NSW 2217, Australia. stephen@oakley.net
Lassere
M N
MN
Portek
I
I
Szomor
Z
Z
Ghosh
P
P
Kirkham
B W
BW
Murrell
G A C
GA
Wulf
S
S
Appleyard
R C
RC
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D011509:Proteoglycans / Q000032:analysis; D015203:Reproducibility of Results; D033081:Shear Strength; D012756:Sheep
D011509:Proteoglycans