Abstract
The aim of this study was to review aspects of the pathobiology of the meniscus in health and disease and show how degeneration of the meniscus can contribute to deleterious changes in other knee joint components. The menisci, distinctive semilunar weight bearing fibrocartilages, provide knee joint stability, co-ordinating functional contributions from articular cartilage, ligaments/tendons, synovium, subchondral bone and infra-patellar fat pad during knee joint articulation. The meniscus contains metabolically active cell populations responsive to growth factors, chemokines and inflammatory cytokines such as interleukin-1 and tumour necrosis factor-alpha, resulting in the synthesis of matrix metalloproteases and A Disintegrin and Metalloprotease with ThromboSpondin type 1 repeats (ADAMTS)-4 and 5 which can degrade structural glycoproteins and proteoglycans leading to function-limiting changes in meniscal and other knee joint tissues. Such degradative changes are hall-marks of osteoarthritis (OA). No drugs are currently approved that change the natural course of OA and translate to long-term, clinically relevant benefits. For any pharmaceutical therapeutic intervention in OA to be effective, disease modifying drugs will have to be developed which actively modulate the many different cell types present in the knee to provide a global therapeutic. Many individual and combinatorial approaches are being developed to treat or replace degenerate menisci using 3D printing, bioscaffolds and hydrogel delivery systems for therapeutic drugs, growth factors and replacement progenitor cell populations recognising the central role the menisci play in knee joint health.
Highlights
Osteoarthritis is responsible for a large and rapidly increasing global disease burden that is challenging health-care systems worldwide
Disease progression in osteoathritis, is marked by increasing pain and loss of joint function, the development of osteoarthritis is usually slow, taking many years from its first mild symptoms to severe debilitating end-stage disease. Progression to this end-state occurs in only a minority of patients with osteoarthritis and disease in many patients remains stable
Several prospective biomarkers have been correlated with various criteria of meniscal pathology including synovial fluid HMGB-1 levels [36,37], inflammatory cytokines and biomarkers of cartilage metabolism 8 years after anterior cruciate ligament (ACL) reconstruction in operated and contralateral knees [38], synovial chemokine expression [34], synovial fluid MMP activity in torn menisci [39] and transcriptomic analysis of synovial extracellular RNA conducted following knee trauma [40]
Summary
Osteoarthritis is responsible for a large and rapidly increasing global disease burden that is challenging health-care systems worldwide. Β-Defensins are significantly upregulated during the inflammatory conditions which are generated in the knee-joint during OA and act in concert with DAMP (damage associated molecular pattern) and PAMP (pathogen associated molecular pattern) receptors such as the Toll-like and NOD-like receptors of the innate immune system which identify lipopolysaccharide and peptidoglycan components on cell membranes of invading organisms [19,20] and this response protects meniscal tissues from microbial invasion [21]. Aquaporin (AQP1) is a specific water transport channel protein expressed by articular chondrocytes, meniscal cells and synoviocytes in the knee-joint which is upregulated during OA and RA [21] This may represent a new molecular target in therapeutic procedures aimed at maintaining the hydration and functional viscoelastic hydrodynamic properties of knee joint tissues during these arthritic conditions [22]
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