Periostin in joint physiology and pathology: multiple roles from mechanisms to clinical perspectives

Joint-related diseases, including osteoarthritis (OA), rheumatoid arthritis (RA), intervertebral disc degeneration (IDD), anterior cruciate ligament (ACL) injury, and shoulder instability, severely compromise human health. Periostin (POSTN), a multifunctional extracellular matrix protein enriched in connective tissues, exerts multifaceted roles in joint biology. It supports normal tissue development, but under pathological conditions, it binds to cell-surface receptors. This interaction activates downstream signaling cascades, such as Wnt/β-catenin, nuclear factor κB (NF-κB), and transforming growth factor β (TGF-β), thereby propelling disease progression. Notably, POSTN's functional specificity is dictated by its splice variant profiles and cellular localization, with the tissue-specific expression and functional divergence of these variants emerging as a pivotal research focus. Recent evidence links POSTN expression levels to the severity of joint-related diseases, highlighting its potential as a diagnostic biomarker. This review summarizes the core roles and underlying mechanisms of POSTN in joint physiology and pathology, laying a theoretical foundation for clinical translation.