The spatial proteome of the human intervertebral disc reveals architectural changes in health, ageing and degeneration

The proteome of the human intervertebral disc, particularly the extracellular matrix, underpins its integrity and function. We describe high quality spatial proteomes from young and aged lumbar discs, profiled across different regions, and identified sets of proteins that are variable or constant with respect to disc compartments, levels, and anatomic directions. From these, four protein modules defining a young disc were derived. Mapping these modules to aged disc proteomes showed that the central nucleus pulposus becomes more like the outer annulus fibrosus. Transcriptome analysis supported these proteomic findings. Concurrently, dynamic proteomic analyses indicate impaired protein synthesis and increased degradative activities. We identified a novel set of proteins that correlates with disc hydration that are predictive of MRI intensities. Signalling pathways (SHH, WNT, BMP/TGFβ) and hypertrophic chondrocyte differentiation events relating to ageing and degeneration were implicated. This work presents the foundation proteomic architectural landscapes of young and ageing human discs.