Abstract
Introduction
Analogous to articular cartilage, changes in spatial chondrocyte organisation have been proposed to be a strong indicator for local tissue degeneration and destruction in the intervertebral disc (IVD). While a progressive structural and functional degradation of the extracellular (ECM) and pericellular (PCM) matrix occurs in osteoarthritic cartilage, these processes have not yet been biomechanically elucidated in the IVD. We aimed to evaluate the local stiffness of the ECM and PCM in the anulus fibrosus of the IVD on the basis of local cellular spatial organisation.
Method
Using atomic force microscopy, we measured the elastic modulus of the local ECM and PCM in human disc samples using the spatial chondrocyte patterns as an image-based biomarker.
Result
By measuring tissue from 30 patients, we found a significant difference in the elastic moduli of the PCM in clusters when compared to the healthy patterns single cells (p=0.029), pairs (p=0.016), and string formations (p=0.010) whereas the values of the elastic moduli of the ECM only reached statistical significance when clusters were compared with string formations. The ECM/PCM ratio ranged from 0.62 to 0.89. Overall, the reduced elastic moduli in clusters demonstrates that cluster formation is not only a morphological phenomenon describing disc degeneration, but it marks a compromised biomechanical functioning.
Conclusion
This study is the first to describe and quantify the differences in the elastic moduli of the ECM in relation to the PCM in the anulus fibrosus of the IVD by means of atomic force microscopy on the basis of spatial chondrocyte organisation. Advanced disc degeneration is accompanied by a biomechanically compromised tissue functioning.
