Abstract
Intervertebral disc (IVD) degeneration is often the cause of low back pain. Degeneration occurs with age and is accompanied by extracellular matrix (ECM) depletion, culminating in nucleus pulpous (NP) extrusion and IVD destruction. The changes that occur in the disc with age have been under investigation. However, a thorough study of ECM profiling is needed, to better understand IVD development and age-associated degeneration. As so, iTRAQ LC-MS/MS analysis of foetus, young and old bovine NPs, was performed to define the NP matrisome. The enrichment of Collagen XII and XIV in foetus, Fibronectin and Prolargin in elder NPs and Collagen XI in young ones was independently validated. This study provides the first matrisome database of healthy discs during development and ageing, which is key to determine the pathways and processes that maintain disc homeostasis. The factors identified may help to explain age-associated IVD degeneration or constitute putative effectors for disc regeneration.
Highlights
A young healthy disc consists of a highly plastic and hydrated region – the nucleus pulposus (NP) – and a network of collagen fibres oriented in sheets around the nucleus – the annulus fibrosus (AF), which provides tensile strength and confines the NP, limiting bulging[6]
Among the proteins within cluster 1B, we found a significant enrichment of Gene Ontology terms related to extracellular matrix, glycosaminoglycan, polyssacharide, carbohydrate, hyaluronic acid and ion binding, as well as cell adhesion and membrane bound organelles
Given that Gene Ontology (GO) analysis revealed enrichment of several extracellular matrix (ECM)-related categories, we examined the overlap of the NP proteomic signature with the matrisome, a comprehensive list of genes coding for ECM molecules and regulators, which is significantly more comprehensive for data mining and for posing questions relevant to matrix biology than GO terms[30]
Summary
A young healthy disc consists of a highly plastic and hydrated region – the nucleus pulposus (NP) – and a network of collagen fibres oriented in sheets around the nucleus – the annulus fibrosus (AF), which provides tensile strength and confines the NP, limiting bulging[6]. Apart from overall matrix breakdown caused by MMPs (matrix metalloproteinases) and ADAMTS (a desintegrin and metalloprotease with thrombospondin motifs) overexpression[7], PG and collagen synthesis patterns[9, 10], as well as fibre crosslinking[1] are altered This inhibits matrix turnover and, together with the already limited repair response, leads to dehydration and progressive ECM disorganization. The availability of oxygen, nutrients and growth factors[12], and the acidity of the environment, as well as the removal of metabolites, are influenced by ECM calcification and impermeabilization[7] With increasing age, this imbalance of the normal homeostatic mechanism impairs normal disc function, in the NP13, resulting in reduced disc height, hernia formation and spinal pain, as nerve roots become compressed[2]. Rapid advances are being made in understanding and regulating the degenerative process, many challenges remain[2]
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