Blocking osteopontin-fibronectin interactions reduce extracellular fibronectin deployment and arthritic immunopathology

Organokines in Rheumatoid Arthritis: A Critical Review

“…Osteocalcin (OCN) is a bone-derived hormone that is synthesized and secreted by osteoblasts and then activated by osteoclasts during bone resorption. It is a key factor responsible for the mineralization of the extracellular matrix, and its serum levels increase dramatically during this process, being used clinically as a marker of osteoblastic bone formation [ 13 , 75 , 76 , 77 , 78 ].…”

“…Thus, serum OCN can enter distant cells to regulate IR, glucose homeostasis, and brain function, with anti-inflammatory and beneficial activity. On the other hand, some studies also claim that OCN can recruit osteoclasts and potentiate their chemotaxis and inhibit osteoblast activity, contributing to osteoclastogenesis and leading to osteoporosis [ 13 , 76 , 77 , 78 , 79 , 80 ].…”

“…With aging, the expression of OPN in the bone marrow stroma is reduced. OPN is closely related to the development of many bone-related diseases, including RA [ 57 , 70 , 73 , 75 , 76 , 81 ].…”

“…The imbalance of Th1/Th2 cells and the levels of secreted cytokines trigger events that lead to chronic inflammation and cartilage and bone destruction. Thus, OPN plays a crucial role in the pathogenesis and progression of RA by affecting the balance of Th1/Th2 cells and also inducing the differentiation of Th17 lymphocytes, affecting IL-17 levels and generating an inflammatory response, with its effects being more pronounced in their phosphorylated form [ 57 , 62 , 70 , 73 , 75 , 76 , 81 , 82 ].…”

“…It was also previously reported that it modulates tissue fibrosis by promoting TGF-β activation and fibronectin expression. Therefore, OPN acts as an important mediator in the maintenance of RA, as it activates synovial macrophages and fibroblasts, which stimulate cartilage and bone matrix degradation by secreting matrix MPPs and pro-inflammatory cytokines such as IL-6 and TNF-α in addition to stimulating fibrosis [ 73 , 75 , 76 , 81 , 82 , 83 ].…”