Osteopontin: A Bone-Derived Protein Involved in Rheumatoid Arthritis and Osteoarthritis Immunopathology

Abstract

Osteopontin (OPN) is a bone-derived phosphoglycoprotein related to physiological and pathological mechanisms that nowadays has gained relevance due to its role in the immune system response to chronic degenerative diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). OPN is an extracellular matrix (ECM) glycoprotein that plays a critical role in bone remodeling. Therefore, it is an effector molecule that promotes joint and cartilage destruction observed in clinical studies, in vitro assays, and animal models of RA and OA. Since OPN undergoes multiple modifications, including posttranslational changes, proteolytic cleavage, and binding to a wide range of receptors, the mechanisms by which it produces its effects, in some cases, remain unclear. Although there is strong evidence that OPN contributes significantly to the immunopathology of RA and OA when considering it as a common denominator molecule, some experimental trial results argue for its protective role in rheumatic diseases. Elucidating in detail OPN involvement in bone and cartilage degeneration is of interest to the field of rheumatology. This review aims to provide evidence of the OPN’s multifaceted role in promoting joint and cartilage destruction and propose it as a common denominator of AR and OA immunopathology.

Exploring the Cellular and Molecular Mechanism of Discoidin Domain Receptors (DDR1 and DDR2) in Bone Formation, Regeneration, and Its Associated Disease Conditions

“…According to a survey, overexpression of DDR2 with partial Function in RA patients increases RA synovial fluid while promoting cartilage-degrading matrix metalloproteases (MMP-1, MMP-2, and MMP-13) [131]. Meanwhile, the overall process of DDR2 depends on the pathophysiologic involvement of RA FLS-influenced DDR2-induced MMP and MMP subclass secretions [132]. RA is a chronic systemic disorder characterized by joint inflammation that leads to bone function loss, a physiology defect.…”

The Multifaceted Role of Osteopontin in Prostate Pathologies

“…OPN is a sialic acid-rich protein, originally identified in the bone extracellular matrix, and can exist as an immobilized or as a soluble protein [22][23][24]. There are several synonyms for OPN, including early T-lymphocyte activation and bone sialoprotein, and it is encoded by the gene SPP1 (secreted phosphoprotein I).…”

Osteopontin, osteoprotegerin and musculoskeletal ultrasound findings in first-degree relatives of rheumatoid arthritis: potential markers of preclinical disease

“…Osteoprotegerin (OPG) regulates bone resorption mainly by inhibiting osteoclastic bone resorption and also promoting osteoclast apoptosis [ 13 ]. OPG works as a decoy receptor, preventing association of receptor activator of nuclear factor-kappa B ligand (RANKL) with RANK receptor [ 14 , 15 ], and thus moderating osteoclastogenesis and bone resorption.…”