Periostin: A candidate mediator of muscle–tendon ECM remodeling in obesity

Obesity is associated with chronic inflammation, metabolic dysregulation, and significant remodeling of particularly muscle and tendon. Emerging evidence implicates periostin (POSTN), a non-structural matricellular protein, as a key mediator of extracellular matrix (ECM) remodeling in response to metabolic and mechanical stressors. POSTN's modular structure enables it to orchestrate ECM architecture by binding collagen, fibronectin, and matrix-modifying enzymes, positioning it as a central modulator of mechanochemical tissue properties. Normally POSTN is expressed at a low level but becomes upregulated during injury and inflammation that are associated with fibrotic responses. In obesity POSTN expression is elevated systemically and locally in adipose, muscle, and tendon tissues, where it may contribute to the maladaptive remodeling through integrin-mediated activation of signaling pathways such as PI3K/Akt and TGF-β/Smad. This promotes collagen deposition, matrix cross-linking, and fibrosis, impairing tissue function and regenerative capacity. Evidence from obesity and muscle injury models suggests that POSTN may act as both a biomarker of, and a therapeutic target for mitigating, fibrotic changes in musculoskeletal tissues. This review highlights POSTN's context-dependent roles and its potential as a mechanistic link between metabolic dysfunction and musculotendinous tissue degeneration in obesity.