The Role of SLPI Gene-Mediated Inflammation in Osteoarthritis

Osteoarthritis (OA) is a degenerative disease of joint tissue characterized by the breaking down of cartilage and resulting changes in synovium and bone. Mechanics and biology interact in a feed-forward manner in that imbalanced joint loading leads to tissue degeneration and vice versa. Amid numerous genetic factors, the Secretory Leukocyte Protease Inhibitor (SLPI) gene encodes a protein that plays a crucial role in inhibiting proteases, modulating inflammation, promoting tissue repair, and regulating immune responses. In the context of OA, SLPI has been identified as a key regulator in joint homeostasis. The release of SLPI in human tissues is augmented by pro-inflammatory factors. Such factors include cytokines released during infection or inflammatory processes, such as interleukins-1 and 6 (IL-1 and IL-6), and tumor necrosis factor alpha (TNF-α) released in many inflammatory rheumatic diseases. In this work, a comprehensive review of SLPI-mediated inflammation in OA, its biological functions, and its association with OA is described, providing a foundation for future investigations into its potential therapeutic use. As there is no effective strategy to treat or prevent OA in clinic, further investigation is encouraged to explore the translational possibility of SLPI for drug development.