SPARC in musculoskeletal tissues: Linking matrix assembly to disease.

Secreted Protein Acidic and Rich in Cysteine (SPARC), also known as osteonectin or BM-40, is a prototypical matricellular protein that regulates the dynamic interplay between cells and the extracellular matrix (ECM). Unlike structural ECM components that primarily provide mechanical support, SPARC functions as a regulatory molecule that modulates cell-matrix communication, collagen fibrillogenesis, and tissue remodeling. In musculoskeletal tissues -including bone, cartilage, skeletal muscle, tendons, and intervertebral discs - SPARC plays essential roles in organizing ECM architecture, maintaining mechanical integrity, and coordinating adaptive responses to mechanical loading. Emerging evidence indicates that SPARC also acts beyond classical ECM regulation by linking ECM organization to intracellular signaling and metabolic pathways. In this review, we summarize the structural features and biological functions of SPARC, with particular emphasis on its roles in skeletal and connective tissues. We discuss its contribution to ECM assembly and cell-matrix interactions across diverse tissue environments. Finally, we highlight emerging concepts linking SPARC to tissue degeneration, inflammation, and aging, and explore its potential as a biomarker and therapeutic target in musculoskeletal disease.