Decline after immobilisation and recovery after remobilisation of synovial fluid IL1, TIMP, and chondroitin sulphate levels in young beagle dogs.
OBJECTIVE
To monitor the concentration of markers of cartilage and synovium metabolism in the knee (stifle) joint synovial fluid of young beagles subjected to immobilisation and subsequent remobilisation.


METHODS
The right hind limb of 17 dogs was immobilised in flexion for 11 weeks. Simultaneously, the contralateral left knee was exposed to increased weight bearing. The remobilisation period lasted 50 weeks. Litter mates served as controls. The concentration in joint lavage fluid of interleukin 1alpha (IL1alpha) was measured by immunoassay, the activity of phospholipase A(2) (PLA(2)) was determined by an extraction method, chondroitin sulphate (CS) concentration by precipitation with Alcian blue, hyaluronan (HA) by an ELISA-like assay using biotinylated HA-binding complexes, matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinases 1 (TIMP-1) by sandwich ELISA, and synovitis was scored by light microscopy.


RESULTS
Synovitis or effusion was absent in all experimental and control groups. Immobilisation decreased the joint lavage fluid levels of IL1alpha (p<0.05), TIMP (p< 0.05), and the concentration of CS down to 38% (p<0.05) in comparison with untreated litter mates with normal weight bearing. Immobilisation did not affect the activity of PLA(2), or the concentration of MMP-3 or HA in synovial fluid. Joint remobilisation restored the decreased concentrations of markers to control levels. Increased weight bearing did not change the concentrations of markers in comparison with the control joints with normal weight bearing.


CONCLUSIONS
11 weeks' joint immobilisation decreased the concentration of markers of cartilage and synovium metabolism in the synovial fluid, and remobilisation restored the concentrations to control levels. The changes in joint metabolism induced by immobilisation, as reflected by the markers, are thus different from those found in osteoarthritis, where increased levels of these markers are associated with enhanced degradation and synthesis. These findings suggest that the change induced in joint metabolism by immobilisation is reversible in its early stages.
Haapala
J
J
Department of Surgery, Kuopio University Hospital, Finland. Jussi.Haapala@phks.fi
Arokoski
J P
JP
Rönkkö
S
S
Agren
U
U
Kosma
V M
VM
Lohmander
L S
LS
Tammi
M
M
Helminen
H J
HJ
Kiviranta
I
I
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002358:Cartilage, Articular / Q000378:metabolism*; D002809:Chondroitin Sulfates / Q000378:metabolism; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D007103:Immobilization / Q000502:physiology*; D007375:Interleukin-1 / Q000378:metabolism; D009068:Movement / Q000502:physiology; D013582:Synovial Fluid / Q000378:metabolism*; D013585:Synovitis / Q000209:etiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D016474:Weight-Bearing / Q000502:physiology
D015415:Biomarkers; D007375:Interleukin-1; D019715:Tissue Inhibitor of Metalloproteinase-1; D002809:Chondroitin Sulfates