Synovial fluid biomarker levels predict articular cartilage damage following complete medial meniscectomy in the canine knee

Abstract

The purposes of this study were to document the histological changes present in the tibial plateaus 12 weeks after complete medial meniscectomy in dogs and to determine if synovial lavage fluid biomarker levels are predictive of the severity ofjoint damage. Twelve adult dogs underwent complete unilateral medial meniscectomy and synovial lavage fluid biomarker levels, including cartilage oligomeric matrix protein (COMP), keratan sulfate (5D4), 3B3(-), and 3B3(+), were measured serially at 4-week intervals. The dogs were euthanized 12 weeks after surgery and each medial and lateral tibial plateau from the meniscectomized and contralateral knees was graded histologically. Histological data were analyzed using principal components analysis, which resulted in 4 factors that explained 70% of the variation in the data. Factor 2 (weighted most heavily by subchondral bone thickness) and Factor 3 (representative o f articular cartilage damage) were significantly affected by compartmental site (P < 0.01 for both). Both of these factors were highest in the medial tibial plateau of the meniscectomized knee, and Factor 3 was significantly higher in this site than in the medial tibial plateau of the contralateral knee ( P < 0.01). Peak levels of all 4 synovial lavage fluid biomarkers occurred at 4 weeks post-meniscectomy and 4-week minus baseline levels of all biomarkers were significantly correlated with the Factor 3 scores. This study demonstrates that significant articular cartilage damage occurs relatively quickly following complete medial meniscectomy in dogs and establishes the content and criterion validity for these synovial fluid lavage biomarkers in canine meniscectomy as surrogate measures of articular cartilage damage.

Ascorbic acid increases the severity of spontaneous knee osteoarthritis in a guinea pig model

“…Synovial fluid COMP concentrations were measured by ELISA in 12-month-old animals at the end of the study (Figure 7). Synovial fluid COMP levels, representative of joint tissue turnover (30), correlated with the severity of histologic disease (r ϭ 0.34, P ϭ 0.02) and plasma ascorbic acid concentration (r ϭ 0.58, P Ͻ 0.0001), and differed significantly among the 3 ascorbic acid dose groups (P Ͻ 0.001). Synovial fluid COMP levels also correlated with plasma ascorbic acid concentrations (r ϭ 0.38, P ϭ 0.04) in the analysis restricted to the mediumand high-dose groups.…”

Absence of posttraumatic arthritis following intraarticular fracture in the MRL/MpJ mouse

“…The MRL/MpJ mice showed no subchondral bone thickening. Increased subchondral bone thickness is seen clinically and has also been observed in various animal models of arthritis (7,33).…”

“…When the mice were killed, ϳ150 l of serum was collected via a retroorbital bleed and cardiac stick for analyses of circulating systemic levels of inflammatory cytokines, TGF␤1, as well as hyaluronic acid (HA) and cartilage oligomeric matrix protein (COMP), which are biomarkers of cartilage metabolism associated with progressive arthritic joint pathology (30)(31)(32)(33). Collected blood was centrifuged at 3,500 revolutions per minute for 15 minutes, and the serum was stored at Ϫ80°C until analyzed.…”

“…The entire joint was sectioned in the coronal plane at a thickness of 6 m. Sections were stained with Safranin O and fast green. Cartilage degeneration was graded in the medial and lateral aspects of both the tibia and the femoral condyles by 3 graders under blinded conditions, and scores were averaged using a previously described modified Mankin scoring scale (maximum score 30) (7,33,34). Scores from each location were summed for each joint for a total score within a range of 0-120.…”

“…COMP has been used successfully to monitor tissue involvement in a rat model of experimental arthritis (47) and has been found to be predictive of cartilage degeneration in a canine meniscectomy model of OA (33). COMP levels were not associated with degenerative changes in the articular cartilage.…”