Abstract
The role of growth factors in the pathogenesis of arthritis has received considerably less attention as compared to proinflammatory cytokines in recent years. This is understandable as it is evident that current anti-tumor necrosis factor-α (TNFα) therapy is efficacious in at least in 60% of the rheumatoid arthritis (RA) patients and when given in combination with methotrexate stops radiological progression of bone erosion. Other proinflammatory cytokines, such as interleukin-1 (IL-1) and IL-17 have also been implicated in the dysregulation of bone and cartilage remodelling characteristic of rheumatoid arthritis (RA) and/or osteoarthritis (OA). The direct effects of anti-cytokine treatment on cartilage pathology are not that easy to determine in humans and it remains to be seen if amelioration of cartilage destruction or better cartilage repair has been accomplished with anti-TNF therapy. A complicating factor is that chondrocytes in RA and OA become non-responsive to insulin-like growth factor-I (IGF-I). IGF-I is the main growth factor for stimulation of chondrocyte proteoglycan and collagen type II synthesis in order to maintain the cartilage matrix integrity. This article reviews our current understanding of the role of IGF-I on cartilage extracellular matrix production and the mechanisms underlying the cause of IGF-I non-responsiveness, and in particular the inhibition of IGF-receptor signalling by suppressor of cytokine signalling (SOCS) proteins. The epigenetic and cytokine-dependent regulation of SOCS expression may give an explanation for the loss of IGF-I signalling in chondrocytes in ageing-related diseases such as OA and RA. Whether IGF-1 is replaceable by other growth factors to maintain the cartilage extracellular matrix will be discussed. It is concluded that in addition to the current use of anti-cytokine therapy in arthritis the IGF-I response of chondrocytes must be restored in order to achieve cartilage matrix repair.
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