Chronic low back pain, often linked to intervertebral disc degeneration (IVDD), fundamentally stems from the dehydration of the disc’s gel-like center, the nucleus pulposus (NP). This review shifts focus to the extracellular matrix, specifically highlighting the critical role of aggrecan in maintaining disc hydration and mechanical function through osmotic pressure.
The research team systematically classifies four hallmark modifications of aggrecan in degenerative discs: 1) a decline in the chondroitin sulfate to keratan sulfate ratio, reducing water-binding capacity; 2) increased enzymatic cleavage of the core protein; 3) decreased core protein production; and 4) exacerbated degradation of hyaluronic acid, which disrupts the matrix structure. These changes converge to cause water loss and functional failure.
The study further integrates upstream drivers, including hypoxia, inflammation, lactic acidosis, and osmotic imbalance, that collectively accelerate these damaging modifications. For diagnosis, the review highlights advanced non-invasive imaging techniques like T2-mapping and glycosaminoglycan chemical exchange saturation transfer (gagCEST), which can detect early aggrecan loss during early-stage degeneration.
Therapeutically, current strategies are categorized into regeneration (e.g., anti-inflammatory hydrogels, stem cell exosomes) and substitution (e.g., aggrecan-mimicking biomaterials). However, most regenerative approaches target single factors. The authors conclude that effective future treatments must be multifunctional, simultaneously addressing the multiple drivers of aggrecan loss to restore disc health.
This review redefines aggrecan degradation as a central, targetable axis in IVDD, offering a clear roadmap for groundbreaking diagnostic and regenerative strategies.
The work titled “Aggrecan remodeling in degenerate discs: Patterns, determinants, measurement, and emerging therapies”, was published on Spine Research (accepted on Oct. 13, 2025).
DOI: 10.1097/br9.0000000000000007