Association of articular cartilage degradation and loss of boundary-lubricating ability of synovial fluid following injury and inflammatory arthritis.
OBJECTIVE
To study the relationship between the boundary-lubricating ability of synovial fluid (SF) and articular cartilage damage in a rabbit knee injury model, to correlate collagen markers of such damage with SF boundary-lubricating ability and elastase activity, and to examine the lubricating ability of SF, together with collagen markers of articular cartilage damage, under the inflammatory conditions of knee joint synovitis (KJS) and rheumatoid arthritis (RA).


METHODS
SF was aspirated weekly from the affected knee joints of 10 adult rabbits following transection of the anterior and posterior cruciate ligaments. The boundary-lubricating ability of SF was determined in vitro using a previously described friction apparatus. Lubricin concentrations and type II collagen (CII) peptides were quantified by sandwich enzyme-linked immunosorbent assays (ELISAs). Levels of the C-terminal neoepitope 9A4 (derived from collagenase degradation of CI, CII, and CIII) and of epitope 5-D-4 of keratan sulfate (a marker of proteoglycan depletion) were quantified by inhibition ELISAs. Elastase activity was measured spectrophotometrically. The sensitivity of purified human lubricin to digestion by neutrophil elastase (NE) was examined by Western blotting.


RESULTS
The lubricating ability of SF from injured rabbit knees was significantly decreased at weeks 2 and 3 compared with week 1 after injury. Lubricin concentrations were significantly higher at week 1 than at weeks 2 and 3. CII peptide concentrations increased significantly at weeks 2 and 3 compared with week 1, while 9A4 neoepitope concentrations increased significantly at week 3 compared with weeks 1 and 2. There were no significant differences in epitope 5-D-4 concentrations among the 3 weeks. Elastase activity in SF increased significantly at weeks 2 and 3 compared with week 1. Elastase activity correlated significantly with diminishing lubrication at weeks 1, 2, and 3. SF from patients with KJS or RA exhibited deficient lubrication and elevated levels of CII peptides compared with SF from normal controls. NE was shown to completely degrade purified human lubricin in vitro.


CONCLUSIONS
Loss of boundary-lubricating ability of SF after injury is associated with damage to the articular cartilage matrix. This can be attributed to inflammatory processes resulting from the injury, particularly in the early phases. This association also exists in patients with acute knee injuries or progressive chronic inflammatory arthritis.
Elsaid
K A
KA
University of Rhode Island, Kingston, RI, USA.
Jay
G D
GD
Warman
M L
ML
Rhee
D K
DK
Chichester
C O
CO
D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries; D001168:Arthritis / Q000209:etiology / Q000503:physiopathology*; D002358:Cartilage, Articular / Q000503:physiopathology*; D024043:Collagen Type II / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007718:Knee Injuries / Q000150:complications / Q000503:physiopathology*; D007719:Knee Joint; D023421:Models, Animal; D010196:Pancreatic Elastase / Q000032:analysis; D011817:Rabbits; D013582:Synovial Fluid / Q000737:chemistry / Q000502:physiology; D013585:Synovitis / Q000209:etiology / Q000503:physiopathology; D000099158:Proteoglycan 4
D024043:Collagen Type II; D006023:Glycoproteins; D010196:Pancreatic Elastase; D000099158:Proteoglycan 4