Abstract
SummaryObjectiveRecent research in knee osteoarthritis (OA) highlights the role of the meniscus in OA pathology. Our aim was to compare the proteomes of medial and lateral menisci from end-stage medial compartment knee OA patients, with reference menisci from knee-healthy deceased donors, using mass spectrometry.DesignTissue plugs of Ø3 mm were obtained from the posterior horns of the lateral and medial menisci from one knee of 10 knee-healthy deceased donors and 10 patients undergoing knee replacement. Proteins were extracted and prepared for mass spectrometric analysis. Statistical analysis was conducted on abundance data that was log2-transformed, using a linear mixed effects model and evaluated using pathway analysis.ResultsWe identified a total of 835 proteins in all samples, of which 331 were included in the statistical analysis. The largest differences could be seen between the medial menisci from OA patients and references, with most proteins showing higher intensities in the medial menisci from OA patients. Several matrix proteins, e.g., matrix metalloproteinase 3 (MMP3) (4.3 times higher values [95%CI 1.8, 10.6]), TIMP1 (3.5 [1.4, 8.5]), asporin (4.1 [1.7, 10.0]) and versican (4.4 [1.8, 10.9]), all showed higher abundance in medial menisci from OA patients compared to medial reference menisci. OA medial menisci also showed increased activation of several pathways involved in inflammation.ConclusionAn increase in protein abundance for proteins such as MMP and TIMP1 in the medial menisci from OA patients suggests simultaneous activation of both catabolic and anabolic processes that warrants further attention.
Highlights
Osteoarthritis (OA) is a chronic joint disease traditionally characterized by loss of articular cartilage and changes in the underlying bone
In order to be included in the statistical analysis, proteins were allowed to have a maximum of one missing value per sample group, which resulted in 331 proteins remaining
We compared the proteome of human meniscal posterior horns from knee-healthy references and end-stage medial compartment knee OA patients
Summary
Osteoarthritis (OA) is a chronic joint disease traditionally characterized by loss of articular cartilage and changes in the underlying bone. Recent research in knee OA has highlighted an important role for the meniscus in OA etiology and pathogenesis1e3. The menisci are two wedge shaped semi-circular fibrocartilage structures interposed between the femoral and tibial condyles in the knee, and their main function is load transmission[2,3]. Studies have reported that damage to the meniscus, which can occur due to acute knee trauma or as a result of gradual degenerative changes, is strongly associated with increased risk for knee OA4e6. Slow degradation of meniscal tissue has been suggested to occur in early stages of OA, little is known of the molecular processes[7,8]. There is very limited understanding of the molecular composition of the meniscus. More knowledge is needed about the meniscus, both in health and OA
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