Increased angiogenesis-osteogenesis coupling in the endplate at early stages of intervertebral disc degeneration

Low back pain is closely linked to intervertebral disc degeneration, with endplate remodeling representing an early and potentially decisive event. Our study investigated whether lumbar spine instability provokes early osteogenesis–angiogenesis coupling in mouse EPs and mapped the three-dimensional spatial relationship between Osterix⁺ cells and CD31highEndomucinhigh (type-H) blood vessels. A lumbar spine instability model in C57BL/6J male and female mice induced early degenerative changes in the cranial endplate, with micro-CT analysis revealing progressive degeneration by 4 weeks and histological sections showing pronounced cartilage sclerosis. To visualize and quantify vascular and osteogenic interactions, we employed a three-dimensional thick-section immunofluorescence imaging technique combined with quantitative spatial correlation analysis optimized for skeletal vasculature mapping. Although the overall type H vessel volume did not increase significantly at these early stages, the number of Osterix⁺ cells was markedly elevated after 4 weeks. Spatial analysis demonstrated that mechanical instability rapidly recruits osteogenic cells to within 20 micrometers of blood vessels, establishing a defined angiogenesis–osteogenesis coupling process. In conclusion, early LSI-induced recruitment of Osterix⁺ cells to type H vessel niches in the cranial endplate initiates ossification and identifies a temporally and spatially explicit window for interventions targeting angiogenesis–osteogenesis coupling to prevent the progression of IVDD.