Osteoarthritis (OA), one of the most common joint disorders, is characterized by chronic progressive cartilage degradation, osteophyte formation, and synovial inflammation. OA lesions are not only located in articular cartilage but also in the entire synovial joint. Nevertheless, most of the early studies done mostly focused on the important role of chondrocyte apoptosis and cartilage degeneration in the pathogenesis and progress of OA. The increased expression of hypoxia-inducible factors (HIF-1α and HIF-2α) is known to be the cellular and biochemical signal that mediates the response of chondrocytes to hypoxia. The role of the synovium in OA pathogenesis had been poorly evaluated. Being sensitive to hypoxia/reoxygeneration (H/R) injury, fibroblast-like synoviocytes (FLS) play an essential role in cartilage degradation during the course of this pathology. Insulin-like growth factor binding protein 3 (IGFBP-3) acts as the main carrier of insulin-like growth factor I (IGF-I) in the circulation and remains the most abundant among the six IGFBPs. Synovial fluids of OA patients have markedly increased levels of IGFBP-3. We aim to discuss the interconnected behavior of IGFBP-3 and synoviocytes during the course of osteoarthritis pathogenesis, especially under the influence of hypoxia-inducible factors. In this review, we present information related to the essential role that is played by IGFBP-3 and mitochondria in synoviocyte-induced osteoarthritis through H/R injury. Little research has been done in this area. However, strong evidences show that the level of IGFBP-3 in synovial fluid significantly increased in OA, inhibiting the binding of IGF-1 to IGFR 1 (IGF receptor-1) and therefore the inhibition of cell proliferation. To the best of our knowledge, this is the first paper providing a comprehensive explanatory contribution of IGFBP-3 and mitochondria in synovial cell-induced osteoarthritis through hypoxia/reoxygenation mechanism.
Essential role of insulin-like growth factor 2 in resistance to histone deacetylase inhibitors