Angiogenesis in ossification of the posterior longitudinal ligament: progress from mechanism to targeted intervention

Ossification of the posterior longitudinal ligament (OPLL) is a degenerative spinal disorder characterized by heterotopic ossification of ligamentous tissue. Its pathogenesis is multifactorial and complex, involving genetic susceptibility, chronic inflammation, mechanical stress, and metabolic dysregulation. In recent years, accumulating evidence has demonstrated that angiogenesis not only supplies essential nutrients and metabolic support to ossified ligament regions but also actively regulates the differentiation of mesenchymal stem cells toward osteogenic and chondrogenic lineages through specific molecular signaling pathways, thereby promoting ectopic bone formation. Focusing on angiogenesis as a central theme, this review systematically summarizes the mechanisms by which key molecules, including LOXL2, Sema3A, integrin αVβ3, ANGPT2, IL-6, TGF-β, the ACE D/D polymorphism, and YAP, mediate the coupling of angiogenesis and osteogenesis in OPLL. Furthermore, we propose angiogenesis-targeted strategies as a potential therapeutic avenue for OPLL, aiming to provide new theoretical insights and directions for both basic research and clinical intervention.