IGFs and IGF-Binding Proteins in the Synovial Fluid of Patients with Rheumatoid Arthritis and Osteoarthritis

Abstract

The progressive damage of human articular cartilage is associated with loss of integrity of its extracellular matrix components. Their metabolism is under the control of cytokines produced locally. It is known that peptide growth factors stimulate chondrocytes to synthesize matrix components, and other cytokines, such as interleukins, promote their catabolism by stimulation of chondrocytes to the production of enzymes degrading components of cartilage. The aim of this study was evaluation the presence of inulin-like growth factors (IGFs) in synovial fluid and blood serum of patients with rheumatoid arthritis and osteoarthritis and their binding proteins and matrix metalloproteinases that regulate their bioavailability using Western Immunoblot, ELISA test and zymography technique. The results showed that both IGFs were present, first of all, in the form of high molecular complexes with their specific binding proteins. In this way those proteins prolonged growth factors' half-life but suppressed their bioavailability for receptors and action on target cells. Low content of free IGF-I indicated limitation of its anabolic influence on cartilage metabolism of patients with both diseases.

Comparison of miRNA cargo in human adipose-tissue vs. amniotic-membrane derived mesenchymal stromal cells extracellular vesicles for osteoarthritis treatment

“…hAMSC-EVs' superior OA protective features also emerged for growth factors [Table 2]. In fact, in a shared scenario of OA driving factors targeting, such as VEGFA, CTGF, EGF, BDNF, and HGF, hAMSC-EVs more actively spotted TGFB1, which, at high and constant levels, as in OA patients, changes from a factor that blocks to a factor that facilitates chondrocyte hypertrophy, together with synovial fibrosis and osteophytes [70] . On the contrary, hASC-EVs more likely target IGF1 and especially IGF2, both having anabolic effects on cartilage, thus further reducing their bioavailability that is already suppressed in OA synovial fluid by the formation of high molecular weight complexes with their specific binding proteins [71] .…”