A variety of destructive enzymes are secreted by pannnus. Prominent among these are the various matrix metalloproteinases (MMPs) and cathepsins. These enzymes act upon collagen and the proteoglycan matrix, thereby destroying the central structure of articular cartilage. Other destructive factors include the cytokines TNF-alpha and IL-1, which activate osteoclasts to resorb subchondral bone. A further important mediator is the recently described osteoclast differentiation factor (ODF) (also referred to as TNF-related activation-induced cytokine [TRANCE], receptor activator of nuclear factor kappaB ligand [RANKL], or osteoprotegerin ligand).
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