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

Robion, F. C.; Doizé, Béatrice; Bouré, Ludovic; Marcoux, M.; Ionescu, Mirela; Reiner, A; Poole, A. Robin; Laverty, Sheila

doi:10.1016/s0736-0266(00)90008-1

Cited by 48 publications

(56 citation statements)

References 50 publications

(48 reference statements)

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“…Aggrecan 846 epitope is present on intact aggrecan molecules (the epitope is associated with chondroitin sulfate chains near the G3 domain in healthy and OA cartilage [20]). Aggrecan 846 is measured by radioimmunoassay (RIA) with a mouse monoclonal IgM antibody, 125 I-labeled fetal human aggrecan as a tracer, and unlabeled fetal bovine aggrecan as a standard (2,21). CPII is cleaved from the procollagen molecule as it forms fibrils (6).…”

Section: Methodsmentioning

confidence: 99%

“…Thus, CPII levels are potentially an index of type II collagen formation and are quantified by an inhibition RIA using 125 I-labeled fetal bovine CPII and a rabbit antiserum (R160) to bovine CPII (6,22). KS, an index of proteoglycan catabolism, was quantified by inhibition RIA using the monoclonal antibody AN9P1 Fab fragment, 125 Ilabeled adult human aggrecan as a tracer, and unlabeled aggrecan as the standard (2,21). The amino-terminal (TC A ) fragment cleaved by collagenase from triple-helical type II collagen includes (at its carboxy terminus) the neoepitope Col2-3/4C long mono , which was measured using a competitive inhibition monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) (7,8,23,24).…”

Section: Methodsmentioning

confidence: 99%

“…The volume increase and accompanying decrease in viscosity indicate marked changes in synovial fluid properties following cruciate ligament transection. Given the lack of knowledge on clearance rates of the markers, it seemed prudent to sample the joint fluid aspirate as completely as possible and to express the results both as a concentration and as the content in the total joint aspirate, as was done previously (21).…”

Section: Body Fluid Biomarkers In Early Experimental Oa 549mentioning

confidence: 99%

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Analysis of cartilage biomarkers in the early phases of canine experimental osteoarthritis

Matyas

Atley

Ionescu

et al. 2004

Arthritis & Rheumatism

140

124

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Objective. To study 3 body fluids for changes in the levels of 5 biomarkers of cartilage metabolism during the early phases of experimental osteoarthritis (OA).Methods. Twenty skeletally mature mixed-breed canines underwent unilateral surgical transection of the anterior cruciate ligament. Samples of joint fluid, serum, and urine were obtained preoperatively and just before necropsy (3 weeks or 12 weeks postoperatively). Biomarkers included 2 markers of cartilage matrix synthesis/turnover (aggrecan 846 epitope and C-propeptide of type II collagen) and 3 markers of cartilage degradation (keratan sulfate proteoglycan epitope, the collagenase-generated cleavage epitope of type II collagen [Col2-3/4C long mono , or CIIC], and crosslinked peptides from the C-telopeptide domain of type II collagen [Col2CTx]). Significant changes in the levels of these biomarkers were determined by paired analyses.Results. Joint pathology was more severe in the 12-week group compared with the 3-week group. In joint fluid, due to limited volume, only Col2-3/4C long mono and Col2CTx were measured. Significant elevations in the levels of both of these markers were observed in experimental joints in both the 3-week group and the 12-week group. In serum, the level of aggrecan 846 epitope was elevated at both 3 weeks and 12 weeks, the level of Col2-3/4C long mono was elevated at 12 weeks, and the level of Col2CTx was elevated at both 3 weeks and 12 weeks. In urine, the level of Col2-3/4C long mono was elevated at 12 weeks after surgery.Conclusion. Levels of biomarkers of intact aggrecan proteoglycan (aggrecan 846 epitope) and type II collagen degradation (Col2-3/4C long mono and Col2CTx) were elevated early after unilateral stifle joint injury, suggesting that these markers are sensitive and specific for early cartilage changes associated with isolated joint injury in this established model of experimental OA.The early stages of osteoarthritis (OA) are difficult to diagnose. Joint structure and function are typically altered substantially before symptoms cause patients to seek medical care, that is, the osteoarthritic process begins long before OA presents as a clinical disease. The insidious onset and "silent" progression of primary OA not only obscure an early diagnosis, but also delay treatment that may help prevent further cartilage destruction and joint failure. Hence, diagnostic tests that can detect and monitor molecular events early in the pathogenesis of OA would be potentially very useful.For nearly a century, synovial fluid analysis has been important in the differential diagnosis of arthritis. Although synovial fluid analysis is useful in distinguishing between inflammatory, septic, and crystal-induced arthritis, its value in OA is limited. Similarly, routine blood and urine analyses can identify certain inflammatory arthritides and metabolic defects that cause joint pain and pathology but, as yet, reveal little about the OA process. No specific molecular markers of the OA process are currently available for clinical use, and the...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Body Fluid Biomarkers In Early Experimental Oa 549mentioning

confidence: 99%

See 1 more Smart Citation

Analysis of cartilage biomarkers in the early phases of canine experimental osteoarthritis

Matyas

Atley

Ionescu

et al. 2004

Arthritis & Rheumatism

140

124

View full text Add to dashboard Cite

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“…Blood samples for drug concentration determination were collected at time 0 (prior to drug administration) and at 15, 30, and 45 min, and 1, 1.5, 2, 2.5, 3,4,6,8,12,18,24,36,48,72,96, and 120 h post administration. Subsequent samples were collected on day 7, 8, 9, and 10 post drug administration.…”

Section: Sample Collectionmentioning

confidence: 99%

Pharmacokinetics of betamethasone in plasma, urine, and synovial fluid following intra‐articular administration to exercised thoroughbred horses

Knych

Stanley

Harrison

et al. 2017

Drug Testing and Analysis

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aThe use of corticosteroids, such as betamethasone, in performance horses is tightly regulated. The objective of the current study was to describe the plasma pharmacokinetics of betamethasone as well as time-related urine and synovial fluid concentrations following intra-articular administration to horses. Twelve racing-fit adult Thoroughbred horses received a single intra-articular administration (9 mg) of a betamethasone sodium phosphate and betamethasone acetate injectable suspension into the right antebrachiocarpal joint. Blood, urine, and synovial fluid samples were collected prior to and at various times up to 21 days post drug administration. All samples were analyzed using tandem liquid chromatography-mass spectrometry. Plasma data were analyzed using compartmental pharmacokinetic modeling. Maximum measured plasma betamethasone concentrations were 3.97 ± 0.23 ng/mL at 1.45 ± 0.20 h. The plasma elimination half-life was 7.48 ± 0.39 h. Betamethasone concentrations were below the limit of detection in all horses by 96 h and 7 days in plasma and urine, respectively. Betamethasone fell below the limit of detection in the right antebrachiocarpal joint between 14 and 21 days. Results of this study provide information that can be used to regulate the use of intra-articular betamethasone in the horse.

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“…For example, keratan sulfate increases in synovial fluid as a marker of articular cartilage catabolism [17]. The 846 epitope of chondroitin sulfate (CS-846) is another indicator of changes in cartilage glycosaminoglycan content, specifically of aggrecan turnover, and it can be measured in SF by immunoassay [18][19][20][21]. In humans, the release of CS-846, normally present in juvenile articular cartilage but almost completely absent from adult cartilage, is closely correlated with aggrecan synthesis [22].…”

Section: Introductionmentioning

confidence: 99%

Concentration of the CS-846 Epitope in Serum and Synovial Fluid of Horses with Different Grades of Osteochondral Fragments in the Carpal Joints

Chávez¹,

Folch²,

Araya³

et al. 2016

Gen Med (Los Angeles)

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The aim of this study was to determine serum and synovial concentrations of the CS-846 epitope of articular cartilage aggrecan, in horses with a radiological diagnosis of osteochondral fragmentation (OF). For this purpose, 20 thoroughbred horses with unilateral radiocarpal or intercarpal OF were used, and 10 clinically and radiologically healthy Thoroughbred horses were assigned to the control group. Serum and synovial concentrations of the CS-846 epitope were measured in both groups by means of ELISA. The concentration of the CS-846 epitope in synovial fluid was significantly higher in carpal joints with moderate articular damage (grade 2 OF) than in the control group or in horses with severe disease (grade 3 and 4 OF). In serum, non-statistical differences in the concentration of the CS-846 epitope were observed between horses with OF and controls. We conclude that the concentration of CS-846 epitope in synovial fluid suggests an increase in cartilage aggrecan synthesis, which may be associated with the presence of moderate clinical disease. The CS-846 epitope concentration in synovial fluid may be a useful biomarker for the study of carpal OF in horses, providing a measure of the balance between cartilage synthesis and degradation in this equine disease.

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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

Cited by 48 publications

References 50 publications

Analysis of cartilage biomarkers in the early phases of canine experimental osteoarthritis

Analysis of cartilage biomarkers in the early phases of canine experimental osteoarthritis

Pharmacokinetics of betamethasone in plasma, urine, and synovial fluid following intra‐articular administration to exercised thoroughbred horses

Concentration of the CS-846 Epitope in Serum and Synovial Fluid of Horses with Different Grades of Osteochondral Fragments in the Carpal Joints

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