Osteoarthrosis: Influence of meniscectomy on articular cartilage
Last reviewed: 23.04.2024
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As mentioned earlier, articular menisci play an important role in the normal function of the joints. Menisci are structures that increase the congruence of articular surfaces of the femoral and tibia, increase lateral stability and improve the distribution of synovial fluid, as well as the exchange of nutrients with articular cartilage. Total or partial meniscectomy leads to a change in the direction of the load on the articular surface of the tibia, resulting in degeneration of the articular cartilage.
The study of the influence of meniscatectomy on the biomechanics of the joint, as well as the induction of degenerative processes in articular cartilage and subchondral bone in animals (usually dogs and sheep) has been devoted to a lot of research. Initially, the researchers produced ectomy of the medial meniscus of the knee joint, but later it turned out that the ectomy of the lateral meniscus leads to a more rapid development of osteoarthritis.
Using lateral meniscatectomy in sheep, S. Little and co-authors (1997) investigated changes in articular cartilage and subchondral bone from several sites of the knee joint. Typical histological findings illustrating induced changes in articular cartilage at 6 months after surgery were cartilage disintegration, a decrease in the concentration of proteoglycans, a decrease in the number of chondrocytes. Under the areas of altered cartilage in the subchondral bone, capillary germination was noted in the zone of calcified cartilage, displacement of the "wavy border" outside and thickening of the spongy substance of the subchondral bone.
In a study by P. Ghosh and co-authors (1998), it was shown that in 9 months after lateral meniscectomy, sheep showed signs of subchondral bone remodeling and an increase in its mineral density secondary to degeneration of the articular cartilage. In areas subjected to an abnormally high mechanical load due to the removal of the lateral meniscus (lateral condyle femur and lateral plate of the tibia), an increased synthesis of dermatan sulfate-containing proteoglycans was detected, although in the cartilage of the medial plate an increase in the synthesis of proteoglycans of the same species was also observed. It turned out that dermatan sulfate-containing proteoglycans are mainly represented by decorin. Its highest concentration was found in the middle and deep zones of the articular cartilage.
Simultaneously with the increase in the synthesis of dermatan sulfate-containing proteoglycans in cartilage zones bearing a high load due to the removal of the lateral meniscus, increased catabolism of aggrecan is revealed, as evidenced by the release of its fragments into the nutrient medium from cartilage explants, as well as high MMP activity and aggrecanase. Since the inflammatory activity in this model of osteoarthritis was minimal, the authors suggested that the source of the enzymes were chondrocytes.
Despite the fact that there are still many unresolved issues, the described studies reveal the possible role of biomechanical factors in the pathogenesis of osteoarthritis. It is clear that chondrocytes are able to "feel" the mechanical properties of their environment, reacting to their changes by synthesis of ECM capable of carrying a large load and thus preventing damage to the cartilage. In young animals, moderate exercise stimulated the synthesis of the VGM-rich Aggrecan. This hypertrophic (or adaptive) phase of chondrocyte response can last several years, providing a stable level of mechanical stress on articular cartilage. However, the disturbance of this balance as a result of increased intensity or duration of the load, or changes in normal joint biomechanics after trauma or surgery, or a decrease in the ability of chondrocytes to enhance the synthesis of ECM in response to an increase in load (with aging), the action of endocrine factors entails significant changes in the cellular and matrix level: the synthesis of proteglycans and collagen type II is inhibited, the synthesis of decorin and collagens of types I, III and X is stimulated. Simultaneously with the change in biosynthesis, catabolism of ECM, as well as the level of MMP and aggrecanase, increases. It is not known how the mechanical loading promotes the resorption of chondrocytes surrounding the ECM by chondrocytes, perhaps this process is mediated by prostanoids, cytokines (such as IL-ip or TNF-a, free oxygen radicals). Here it is necessary to mention the role of synovitis in osteoarthritis, since the most likely source of the aforementioned mediators of catabolism can be macrophage-like synovitis and leukocytes infiltrating the synovial membrane of the joint.
In a study by OD Chrisman and co-authors (1981), it was shown that traumatic joint damage stimulates the production of the precursor of prostaglandins, arachidonic acid. The source of arachidonic acid is the membranes of damaged chondrocytes. It is well known that arachidonic acid is rapidly converted into prostaglandins by enzymatic cyclooxygenase (COX). It has been demonstrated that prostaglandins, in particular PGE 2, interact with chondrocyte receptors, altering the expression of their genes. However, it remains unclear whether arachidonic acid stimulates or inhibits the production of proteinases and aggrecanases. Earlier studies have shown that PGE- 2 increases MMP production and causes degradation of articular cartilage. Based on the results of other studies, PGE 2 has an anabolic effect on ECM, and also promotes the integrity of ECM, inhibiting the production of cytokines by chondrocytes. Perhaps, the opposite data of these studies are due to different concentrations of PGE- 2, which were used in them.
A small amount of IL-1p (the main cytokine that stimulates the synthesis and release of MMP, as well as the inhibitory activity of their natural inhibitors) may be formed in response to damage to the articular cartilage, leading to further tissue degradation.
Thus, the studies described in this section have shown that maintaining a subthreshold dynamic load on the joint causes the reproduction of chondrocytes that are capable of transferring new mechanical conditions, which means the onset of the hypertrophic stage of osteoarthritis. Hypertrophied chondrocytes are cells that are in the last stage of differentiation, and therefore, the expression of the genes of the basic elements of the matrix in them is changed. Therefore, the synthesis of aggrecan proteoglycans and type II collagen is inhibited, and the synthesis of decorin, collagen I, III, and Xtypes is increased.
Reduction of the content of aggrecan and type II collagen in ECM, associated with imbalance between the processes of synthesis and degradation, informs articular cartilage the property of inadequately responding to mechanical stress. As a result, chondrocytes become unprotected, the process passes to the third, catabolic, stage, characterized by excessive proteolytic activity and secretion of autocrine and paracrine regulatory factors. Morphologically, this stage is characterized by destruction of ECM of articular cartilage, clinically it corresponds to manifest osteoarthrosis. This hypothesis, of course, is a simplified vision of all complex processes occurring in osteoarthritis, but it generalizes the modern concept of the pathobiology of osteoarthritis.
[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12]