7 research outputs found
Physiological type I collagen organization induces the formation of a novel class of linear invadosomes
This study shows that fibrillar collagen I is the physiological inducer of a novel class of invadosomes, which we named “linear invadosomes.” They are dependent on the scaffold protein Tks5 and are able to degrade extracellular matrix elements. Moreover, we demonstrate that they are β1- and β3-integrin independent, unlike classical invadosomes
The pathophysiology of osteoarthritis
Osteoarthritis (OA) is a complex disease whose pathogenesis includes the contribution of biomechanical and metabolic factors which, altering the tissue homeostasis of articular cartilage and subchondral bone, determine the predominance of destructive over productive processes. A key role in the pathophysiology of articular cartilage is played by cell/extra-cellular matrix (ECM) interactions, which are mediated by cell surface integrins. In a physiologic setting, integrins modulate cell/ECM signaling, essential for regulating growth and differentiation and maintaining cartilage homeostasis. During OA, abnormal integrin expression alters cell/ECM signaling and modifies chondrocyte synthesis, with the following imbalance of destructive cytokines over regulatory factors. IL-1, TNF-alpha and other pro-catabolic cytokines activate the enzymatic degradation of cartilage matrix and are not counterbalanced by adequate synthesis of inhibitors. The main enzymes involved in ECM breakdown are metalloproteinases (MMPs), which are sequentially activated by an amplifying cascade. MMP activity is partially inhibited by the tissue inhibitors of MMPs (TIMPs), whose synthesis is low compared with MMP production in OA cartilage. Intriguing is the role of growth factors such as TGF-beta, IFG, BMP, NGF, and others, which do not simply repair the tissue damage induced by catabolic factors, but play an important role in OA pathogenesis