IGFBP-6 as a potential therapeutic target in musculoskeletal disorders

INTRODUCTION: Insulin-like Growth Factor Binding Protein 6 (IGFBP-6) is a member of the IGFBP family with unique and relevant biological properties. Emerging evidence suggests that IGFBP-6 plays a critical role in musculoskeletal homeostasis and pathology, insulin-like growth factor (IGF)-dependent mechanisms to include IGF-independent effects on cell proliferation, migration, and differentiation. IGFBP-6 is implicated in the regulation of inflammatory and fibrotic processes within articular tissues and tendons, influencing disease onset and progression. AREA COVERED: This review explores current knowledge on the molecular and cellular functions of IGFBP-6 in bone, muscle, articular cartilage and tendon biology, highlights its contribution to degenerative and reparative mechanisms, and discusses its potential as a biomarker and therapeutic target in musculoskeletal disorders of humans, laboratory animals, and domestic animals. EXPERT OPINION: IGFBP-6 is expected to shift from a peripheral IGF modulator to a key node in musculoskeletal homeostasis as a result of the convergence of mechanical and extracellular signaling paradigms. A new avenue for focused intervention is defined by its junction with extracellular vesicle-mediated communication and IGF/SHH signaling. A new class of mechano-epigenetic modulators for fibrotic and articular diseases could be introduced by IGFBP-6-based therapies, which capitalize on its extracellular accessibility and domain-specific versatility.