Osteopontin in Chronic Inflammatory Diseases: Mechanisms, Biomarker Potential, and Therapeutic Strategies.

Chronic inflammatory diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), atherosclerosis, and inflammatory bowel disease (IBD), pose major global health concerns. These disorders are marked by persistent inflammation, immune system dysfunction, tissue injury, and fibrosis, ultimately leading to severe organ dysfunction and diminished quality of life. Osteopontin (OPN), a multifunctional extracellular matrix protein, plays a crucial role in immune regulation, inflammation, and tissue remodeling. It promotes immune cell recruitment, stimulates pro-inflammatory cytokine production, and contributes to fibrosis through interactions with integrins and CD44 receptors. Additionally, OPN activates key inflammatory pathways, including NF-κB, MAPK, and PI3K/Akt, further aggravating tissue damage in chronic inflammatory conditions. Our review highlights the role of OPN in chronic inflammation, its potential as a biomarker, and its therapeutic implications. We explore promising preclinical approaches, such as monoclonal antibodies, small molecule inhibitors, and natural compounds like curcumin, which have demonstrated potential in mitigating OPN-driven inflammation. However, challenges persist in selectively targeting OPN while maintaining its essential physiological roles, including bone remodeling and wound healing. Our review offers insights into therapeutic strategies and future research directions.