Die Rolle des TGF-β-Signalwegs in humanen Meniskusprogenitorzellen und im Meniskusgewebe

In this dissertation it could be shown for the first time the TGF-s-pathway and its Smad signaling molecules inside of meniscus-progenitor-cells (MPC).  This was demonstrated at gene- and protein-level, as well as at cellular- and tissue-level. Moreover at gene- and protein-level it could be shown, that the signaling molecules Smad2, Smad3 and Smad4 show an increased expression in MPCs which remains from less diseased meniscus tissue in comparison to the MPCs from the highly diseased meniscus tissue. These results could be an evidence  for a protective function of the TGF-s-signalling-pathway in the course of degenerative processes of the meniscus tissue. For a better understanding of the TGF-s-signaling-pathway and its Smad-signaling molecules, we performed an overexpression of some Smad molecules inside the MPCs and observed the effects on the Collagen Type I- and Collagen Type II synthesis. Through this overexpression-experiment we observed an increase for Collagen Type I- and for Collagen Type II- synthesis. These findings confirm the assumption, that the TGF-s-pathway has a critical protective function during the meniscus degeneration. The increased production of extracellular matrix components counteracts the degeneration processes inside the meniscus tissue. A healthy or  regenerated meniscus has a biomechanical protective function for the knee joint and counteracts an osteoarthritis. In future the TGF-s-signaling-pathway could represent a potential intervetion-point for the therapeutic treatment of meniscus lesions. Meniscus lesions are frequently associated directly with an osteoarthritis of the knee joint. Threfore the TGF-s-signaling, which enhances the regeneration of meniscus tissue, plays a critical role in prevention of the osteoarthritis in the knee joint.