Identification of extracellular matrix proteins in plasma as a potential
biomarker in the diagnosis of intervertebral disc degeneration
Purpose: At the molecular level, disc degeneration (DD) has been
associated with dissociation of matrix assembly, leading to the loss of
structural integrity. As a result of matrix dissociation, tissue ECM
proteins are expected to leak into the newly developed blood vessels
that circulate in the peripheral blood, indicating diseased states.
Experimental design: To identify the IVD tissue-ECM proteins leaked into
diseased plasma, global proteomic analysis was performed on 10 healthy
volunteers (HV) and 10 diseased subjects (DS) after depletion of highly
abundant proteins such as Albumin and IgG. Results: 28 proteins were
identified as matrix-associated proteins identical to the proteins found
in intervertebral disc tissues. Of these, 26 were from DS and 21 from
HV. Among these candidates, aggrecan and fibulin 1 were found to be up
and downregulated significantly in the DS group. Interestingly, diseased
plasma had a specific expression of COL2A1, native to the nucleus
pulposus. Conclusions and clinical relevance: The upregulated and unique
presence of aggrecan and collagen type 2A1 respectively in diseased
plasma remains indicative of intervertebral disc disease progression.
This identification could aid in understanding the altered protein
signature that remains indicative of tissue damage and the circulation
of damaged tissue products.