Mechanotransduction in meniscal tissue

Knee injuries are very common among young people due to sport activity and in the older population due to fatigue of material. One of the common types of knee injury is a torn meniscus. Since the meniscus is poorly vascularized, most of the tears do not qualify for repair and are treated with partial meniscectomy. Following meniscectomy, patients typically develop osteoarthritis (OA). Meniscal tissue is a major structure in the knee joint involved in load transmission. In this study a three dimensional finite element model of the human knee was used to simulate varying degrees of partial meniscectomy. It was shown that meniscectomy changes the load environment in the knee. The meniscus is a mechanically sensitive tissue and changes in load will likely cause an imbalance in the chemical environment resulting in catabolic pathways which cause tissue degradation. In the second part of this study the biochemical response of the tissue to pathological and physiological loading was measured. Particularly, the interlukin-1 pathway was studied since it is recognized as a promoter of catabolic processes which result in knee degradation. As a result of overloading, increased gene expression of three metalloproteinase's (MMP-1, MMP-3 and MMP-13), which are matrix cleavage proteins was followed by increases in proteoglycan (PG) break down. Next, the IL-1 signaling pathway was blocked to inhibit the catabolic response of the tissue to overloading. The over expression of MMP-3 was suppressed in samples treated with IL-1 signaling inhibitor, which paralleled with decreases in the PG break down.; We showed that partial meniscectomy changes the mechanical environment on the remaining meniscal tissue. Overloading, which can result from partial meniscectomy, starts activation of catabolic molecules via IL-1 pathways. These degradation processes can be suppressed with IL-1 signaling inhibitors.; Motivation of the study. The main goal of this study is to extend our knowledge in field of mechanotransduction in meniscal tissue. This may result in an opportunity to prevent the development of osteoarthritis in meniscectomized knees by preservation of the meniscus structure. The meniscus plays a major role in load transmission in the knee joint. Removing a portion of the meniscus during partial meniscectomy changes the physical environment in the knee joint, leading to an imbalanced biochemical environment and activated catabolic pathways which can further cause tissue degradation.; Additionally, we hope to extend the knowledge on partial meniscectomy surgery so as to guide surgeons in the future. By simulation of varying degrees of meniscectomy we can quantify changes in the loading environment and compare them with the intact case to help understand further consequences and possible complications following such surgery.