Changes in cartilage proteoglycan aggrecan after intra-articular injection of interleukin-1 in rabbits: studies of synovial fluid and articular cartilage.
OBJECTIVE
To determine how acute but transient inflammation affects the cartilage proteoglycan aggrecan and the value of analyses of synovial fluid to study this.


METHODS
For 96 hours after a single intra-articular injection of rabbit knees with human interleukin-1 alpha (IL-1 alpha) or vehicle, articular cartilage and synovial fluid were examined using a putative indicator of aggrecan synthesis (aggrecan chondroitin sulphate epitope 846), immunoreactive keratan sulphate, and total glycosaminoglycan (GAG) content. Aggrecan extractability (with 0.5 M NaCl) followed by 4 M guanidine hydrochloride extraction permitted analyses of cartilage damage, total content and aggrecan heterogeneity. Aggrecan epitopes as well as GAG were assayed in synovial fluid. Changes were related to total joint leucocyte content in synovial fluid.


RESULTS
At 10 ng, IL-1 alpha produced a transient increase in synovial fluid leucocytes at six hours and 24 hours. This accompanied a reduction in content and increased extractability of GAG, which was greatest in the tibial medial compartment of the knee. Further studies of this compartment showed no change in keratan sulphate epitope content, but a transient increase in extractability in 0.5 M NaCl. Epitope 846 content and extractability were unchanged. Total contents and extractability for GAG were inversely correlated in both controls and joints injected with IL-1 alpha. These changes were accompanied by transient increases in GAG, keratan sulphate epitope, and 846 content in synovial fluid.


CONCLUSIONS
According to the aggrecan component measured, damage to the matrix of articular cartilage was sometimes reflected by a transient increased extractability and a net loss of aggrecan. There was always an increased release of GAG, and keratan sulphate, and 846 epitopes into synovial fluid. These studies show that changes in aggrecan epitopes and GAG in synovial fluid reflect changes in cartilage metabolism induced by acute transient inflammation.
Lundberg
C
C
Department of Pharmacology, Pharmacia Pharmaceutials Uppsala, Sweden.
Asberg
I
I
Ionescu
M
M
Reiner
A
A
Smedegård
G
G
Poole
A R
AR
D053674:Aggrecans; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002809:Chondroitin Sulfates / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D016326:Extracellular Matrix Proteins; D005269:Femur; D006025:Glycosaminoglycans / Q000378:metabolism; D007270:Injections, Intra-Articular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007632:Keratan Sulfate / Q000378:metabolism; D037181:Lectins, C-Type; D007958:Leukocyte Count; D008297:Male; D011509:Proteoglycans / Q000378:metabolism*; D011817:Rabbits; D013582:Synovial Fluid / Q000166:cytology*; D013977:Tibia
D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D007375:Interleukin-1; D037181:Lectins, C-Type; D011509:Proteoglycans; D002809:Chondroitin Sulfates; D007632:Keratan Sulfate