Insulin Like Growth Factor

Insulin-like growth factor-1, also known as somatomedin C, was first discovered as a serum factor controlling sulfate incorporation by articular cartilage in vitro. Later studies showed that IGF-1, by promoting the synthesis of type II collagen and aggrecan, induces and maintains the chondrocyte phenotype in vitro. It also promotes chondrocyte survival, but does not act as a mitogen unless combined with FGF-2 or BMP-7 [123,126]. Chondrocytes from animals with experimental arthritis and from patients with OA are hyporesponsive to IGF-1, notwithstanding normal or increased IGF-1 receptor levels. This has been attributed to increased levels of IGFBPs that may interfere with IGF-1 [99]. Because disturbances in the balance between IGF-1 and IGFBPs in OA joints may contribute to defective chondrocyte responses to IGF-1, small molecule inhibitors to restore IGF-1/IGFBP equilibrium have been proposed for the treatment of OA [44]. An additional mechanism may involve IGF-1-mediated upregulation of the type 2 IL-1 decoy receptor (IL-1RII), which is downregulated in OA chondrocytes and binds to IL-1a or IL-1P, but does not transmit intracellular signals [230]. IGF-1 desensitization may also be due to IL-1-induced suppression of cytokine signaling 3 (SOCS3), which inhibits IGF-1 signaling by reducing phosphorylation of the insulin receptor substrate-1 (IRS-1) [203]. Overproduction of nitric oxide may also contribute to IGF-1 resistance by chondrocytes [122,212].

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Arthritis Joint Pain

Arthritis Joint Pain

Arthritis is a general term which is commonly associated with a number of painful conditions affecting the joints and bones. The term arthritis literally translates to joint inflammation.

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