Abstract
BackgroundTo explore potential biomarkers in a meniscectomy-induced knee osteoarthritis model, at forty years after meniscectomy.MethodsWe carried out a forty-year study of 53 patients who, as adolescents, underwent open total meniscectomy and assessed two potential synovial and serum biomarkers, namely glycosaminoglycan (GAG) and matrix metalloproteinase-3 (MMP-3). Of the 30 patients available for review, 8 had contralateral knee operations and were excluded.Of the remaining 22 patients, 17 had successful operated knee synovial fluid aspirations and 8 also had successful contralateral control knee aspirations. GAG and MMP3 levels in the synovial fluid and peripheral serum was measured using Alcian blue precipitation and ELISA quantification, respectively. Patients also had their knee radiographs assessed and their radiographic osteoarthritis classified as per the Kellgren-Lawrence and Ahlbӓck systems.ResultsAt forty years after meniscectomy, synovial MMP-3 levels remain increased (p = 0.0132) while GAG levels were reduced (p = 0.0487) when compared to controls and these two levels correlate inversely. Furthermore, levels of synovial MMP-3 significantly correlated (p = 0.0032, r = 0.7734; p = 0.0256, r = 0.5552) and GAG levels significantly inversely correlated (p = 0.0308, r = − 0.6220; p = 0.0135, r = − 0.6024), respectively, with both radiological scoring systems. Interestingly, we found that the levels of serum MMP-3 correlated only with the synovial fluid levels of MMP-3 in the operated knee and not with the non-operated joint (p = 0.0252, r = 0.7706 vs. p = 0.0764, r = 0.6576). Multiple regression analysis for patient’s quality of life based on these biomarkers revealed an almost perfect result with an R2 of 0.9998 and a p value = 0.0087.ConclusionOur results suggest that serum levels of MMP3 could be used as a potential biomarker for knee osteoarthritis, using a simple blood test. Larger cohorts are desirable in order to prove or disprove this finding.
Highlights
To explore potential biomarkers in a meniscectomy-induced knee osteoarthritis model, at forty years after meniscectomy
Paired analysis of the levels of matrix metalloproteinase-3 (MMP-3) in the synovial fluid revealed that even at this late time point after surgery, the levels of MMP3 are significantly higher in the operated knee (p = 0.0132) (Fig. 2a), with synovial GAGs levels in the operated joint significantly reduced (p = 0.0487) (Fig. 2b)
There was an inverse correlation between the levels matrix metalloproteinases (MMPs)-3 and GAGs levels within the synovial fluid when comparing all 16 samples from both operated and non-operated knees (p = 0.0458, r = − 0.73810) (Fig. 2c)
Summary
To explore potential biomarkers in a meniscectomy-induced knee osteoarthritis model, at forty years after meniscectomy. It is evident that these investigations demonstrate established disease, inadequate for early identification of the condition, which does not always correlate with patients’ perception of symptoms or progression of the condition (Lohmander, 2004; Lawrence et al, 1966; Hannan et al, 2000). This may be attributed to the avascular and aneural nature of articular cartilage, suggesting that patients presenting with symptomatic osteoarthritis often have significant and irreparable cartilage damage, resulting in knee arthroplasty as a definitive solution. Several molecules have been proposed as possible biomarkers of OA two of these being glycosaminoglycans (GAGs) and matrix metalloproteinases (MMPs)
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