PRG4

PRG4, also known as proteoglycan 4 or lubricin, is a gene and the protein it encodes. Lubricin is a large, secreted, mucin-like glycoprotein produced mainly by synovial fibroblasts and by the superficial zone chondrocytes of articular cartilage. It accumulates in synovial fluid and adsorbs to the surfaces of articulating cartilage to form a boundary lubrication layer that reduces friction between opposing joint surfaces during movement. This lubrication helps protect cartilage from wear, limits protein adsorption to cartilage surfaces, and can modulate cell–surface interactions within the joint.

Mutations in PRG4 cause Camptodactyly-Arthropathy-Coxa vara-Pericarditis (CACP) syndrome, an autosomal recessive disorder characterized by noninflammatory joint stiffness, early camptodactyly, hip deformities, and sometimes pericardial effusion. In other conditions such as osteoarthritis and synovitis, lubricin levels in synovial fluid are reduced or dysfunctional, and animal studies suggest that replacement or augmentation of PRG4 can reduce friction and cartilage damage in damaged joints.

The PRG4 gene is conserved across mammals; expression is highest in joints, and regulation is responsive to mechanical loading. Researchers are exploring lubricin replacement therapies, gene therapy to restore PRG4 in affected joints, and biomaterial coatings that mimic lubricin's boundary lubrication.