Use of synovial fluid markers of cartilage synthesis and turnover to study effects of repeated intra-articular administration of methylprednisolone acetate on articular cartilage in vivo.
In vivo the effects of intra-articular (IA) corticosteroids on articular cartilage remain controversial. This study was designed to examine this issue using synovial fluid (SF) markers of cartilage metabolism. Paired radiocarpal joints, without clinical or radiographic signs of joint disease, were studied in 10 adult horses. Aseptic arthrocentesis was performed weekly for 13 weeks. IA injections of methylprednisolone acetate (MPA) into the treatment joint and the vehicle into the control joint were performed at weeks 3, 5 and 7. We used radioimmunoassays on SF samples which measure a keratan sulfate epitope (KS) and the 846 epitope on cartilage aggrecan (PG) and the C-propeptide (CPII) of cartilage type II procollagen which is released following synthesis of this molecule. Gel chromatography was performed on selected SF samples to evaluate the sizes of SF PG molecules. The total joint KS and the 846 epitopes were both present on a heterogeneous population of mainly molecules which, from chromotographic analysis, appeared to be mainly fragments of the articular cartilage aggrecan. They were significantly elevated in MPA joints whereas CPII was significantly reduced compared to the control during the treatment period. These results indicate that the repeated use of IA MPA leads to a potentially harmful inhibition of procollagen II synthesis and an increased release of degradation products of the PG aggrecan from articular cartilage.
Robion
F C
FC
Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St Hyacinthe, Que, Canada.
Doizé
B
B
Bouré
L
L
Marcoux
M
M
Ionescu
M
M
Reiner
A
A
Poole
A R
AR
Laverty
S
S
D053674:Aggrecans; D000818:Animals; D015415:Biomarkers; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects* / Q000254:growth & development*; D002850:Chromatography, Gel; D003094:Collagen / Q000378:metabolism; D024043:Collagen Type II; D000939:Epitopes; D016326:Extracellular Matrix Proteins; D005260:Female; D006736:Horses; D007270:Injections, Intra-Articular; D007632:Keratan Sulfate / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077555:Methylprednisolone Acetate; D011509:Proteoglycans / Q000276:immunology / Q000378:metabolism; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism*
D053674:Aggrecans; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D024043:Collagen Type II; D000939:Epitopes; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; C040072:chondrocalcin; D000077555:Methylprednisolone Acetate; D003094:Collagen; D007632:Keratan Sulfate; D008775:Methylprednisolone