Abstract
Intervertebral disc degeneration is accompanied by a loss of Extra-cellular matrix (ECM) due to an imbalance in anabolic and catabolic pathways. Identifying ECM proteins with anabolic and/or regenerative potential could be the key to developing regenerative therapies. Since human fetal discs grow and develop rapidly, studying these discs may provide valuable insights on proteins with regenerative potential. This study compares core matrisome of 9 fetal and 7 healthy adult (age 22–79) nucleus pulposus (NP), using a proteomic and bioinformatic approach. Of the 33 upregulated proteins in fetus NP’s, 20 of which were involved in ECM assembly pathways: fibromodulin, biglycan, heparan sulfate proteoglycan 2, chondroitin sulfate proteoglycan 4, procollagen C-endopeptidase enhancer and Collagen—type 1a1, 1a2, 6a1, 6a3, 11a1, 11a2, 12a1, 14a1 and 15a1. Moreover, 10 of the upregulated proteins were involved in growth pathways ‘PI3L-Akt signaling’ and ‘regulation of insulin like growth factor transport and uptake.’ Thrombospondin 1,3 and 4, tenascin C, matrilin-3, and collagen- type 1a1, 1a2, 6a1, 6a3 and 9a1. Additionally, matrillin-2 and ‘Collagen triple helix repeat containing 1’ were identified as possible regenerative proteins due to their involvement in ‘Regeneration’ and ‘tissue development’ respectively. In conclusion, the consistency of human fetal NP’s differs greatly from that of healthy adults. In view of these outcomes, the core matrisome of human fetal discs contains an abundant number of proteins that could potentially show regenerative properties, and their potential should be explored in future machinal experiments.
Highlights
Intervertebral disc degeneration is accompanied by a loss of Extra-cellular matrix (ECM) due to an imbalance in anabolic and catabolic pathways
The intervertebral disc (IVD) consists of three major components: firstly, the nucleus pulposus (NP), which is a gel-like structure located at the inner part of the IVD; secondly, the annulus fibrosus (AF), a fibrous structure which is layered around the NP, and at last, the cartilage endplate (CEP), which is a thin cartilage sheet between the disc and the vertebral b ody[1]
The quantitative analysis revealed that 48% of the fetal NP proteome consisted of ECM proteins, the remaining 52% was characterized as cellular
Summary
Intervertebral disc degeneration is accompanied by a loss of Extra-cellular matrix (ECM) due to an imbalance in anabolic and catabolic pathways. The consistency of human fetal NP’s differs greatly from that of healthy adults In view of these outcomes, the core matrisome of human fetal discs contains an abundant number of proteins that could potentially show regenerative properties, and their potential should be explored in future machinal experiments. Proteins and genetic therapeutic options are being explored for regenerative potential in disc degeneration using animal models and in-vitro culture methods Their successfully integration in to human clinical practice is challenged by the intricate biology and homeostatic mechanisms of nucleus pulposus. Since fetal discs undergo rapid growth, their ECM proteome contain many proteins involved in anabolic pathways. Identification of these proteins could give rise to new insights in the pathophysiology and regenerative treatment strategies which revolve around the restorement of ECM in both quantity and quality
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