Decrease in expression of bone morphogenetic proteins 4 and 5 in synovial tissue of patients with osteoarthritis and rheumatoid arthritis

In patients with rheumatoid arthritis (RA), joint pathology is mediated by typical changes in the synovial tissue. Hyperplasia of the synovial lining layer, infiltration of mononuclear cells into the sublining layer, activation of fibroblast-like synoviocytes and the production of catabolic mediators such as IL-1β, TNF-α and matrix metalloproteinases are involved in the joint destruction of patients with RA [1]. Although secondary, synovitis is also found in osteoarthritis (OA) as a response of cartilage degradation and irritation of the lining cells with cartilage matrix components. Eventually, this also induces thickening of the lining layer and aggravates the damage of articular cartilage by the release of inflammatory cytokines and destructive proteases [2].Increases in knowledge about inflammatory cytokines and cytokine networks in chronic joint diseases has promoted the development of a new generation of biological drugs now available as inhibitors of TNF, IL-1 and others. However, little is known about mechanisms that protect and regenerate joints, although it has been shown that the progress of chronic joint diseases is decisively determined by the balance of anabolic and catabolic activities [3,4].Bone morphogenetic proteins (BMPs) are anabolic candidates with pleiotropic functions in the development, homeostasis and repair of various tissues. Current approaches focus mainly on their ability to regenerate bone and cartilage by the induction of differentiation, apoptosis and proliferation of undifferentiated cells as well as by the stimulation of extracellular matrix formation [5,6]. These stimulatory properties led to the clinical use of recombinant BMP-7 in the treatment of bone nonunions [7]. In contrast, BMP signaling has been shown to be involved in the onset and progression of ankylosing enthesitis in spondyloarthropathies and in the induction of osteophytes in OA [8,9]. Antagonism of BMP signaling was therefore suggested as an attractive therapeutic p