Profiling extra cellular matrix associated proteome of human fetal nucleus pulposus in search for regenerative targets

Shanmuganathan Rajasekaran,Muthurajan Raveendran,Niek Djuric,Chitra Thangavel,Dilip Chand Raja Soundararajan,K S Sri Vijay Anand,Monica Steffi Matchado,Krishna Venkateshwaran,Sharon Miracle Nayagam

doi:10.1038/s41598-021-97620-w

Abstract

Degeneration of the intervertebral disc is associated with a decrease in extra-cellular matrix (ECM) content due to an imbalance in anabolic and catabolic signaling. Our previous study profiled the core matrisome of fetal NP’s and identified various proteins with anabolic potential for regenerative therapies. This study aims to complement those results by exploring ECM regulators, associated proteins and secreted factors of the fetal nucleus pulposus (NP). Proteomic data of 9 fetal, 7 healthy adults (age 22–79), and 11 degenerated NP’s was analyzed. Based on the selection criteria, a total of 45 proteins were identified, of which 14 were uniquely expressed or upregulated in fetus compared to adult NP’s. Pathway analysis with these proteins revealed a significant upregulation of one pathway and two biological processes, in which 12 proteins were involved. Prolyl 4 hydroxylase (P4HA) 1 and 2, Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) 1, and Heat shock protein 47 (SERPINH1) were involved in ‘collagen biosynthesis’ pathway. In addition, PLOD 1, SERPINH1, Annexin A1 and A4, CD109 and Galectin 3 (LGALS3) were all involved in biological process of ‘tissue development’. Furthermore Annexin A1, A4 and A5, LGALS-3 and SERPINF1 were featured in ‘negative regulation of cell death’. In conclusion, additionally to core ECM proteome, this study reveals ECM regulators and ECM affiliated proteins of interest to study for regenerative therapies, and their potential should be validated in future mechanistic experiments.

Highlights

Degeneration of the intervertebral disc is associated with a decrease in extra-cellular matrix (ECM) content due to an imbalance in anabolic and catabolic signaling
Even though low back pain can be caused by a great variety of underlying pathologies, most complaints will come from intervertebral disc degeneration (DD)
We explored the core matrisome (ECM proteome) of human fetal nucleus pulposus (NP) for proteins of regenerative potential and found a great number of such proteins to be upregulated or

Summary

Introduction

Degeneration of the intervertebral disc is associated with a decrease in extra-cellular matrix (ECM) content due to an imbalance in anabolic and catabolic signaling. Our previous study profiled the core matrisome of fetal NP’s and identified various proteins with anabolic potential for regenerative therapies. Recent studies have explored the underlying molecular mechanism and proteomic signature of DD4, 7, 8 They found that the decrease in height and loss of water could be attributed to a loss of extracellular matrix proteins[4], and in particular due to a loss in proteoglycans, which are responsible for remaining the hydrostatic pressure of the disc[3]. The majority of the research that focuses on regenerative therapies, study degenerated discs in comparison with healthy d iscs[6,7,8] Even though this approach will nicely quantify the differences and reveal areas of special interest. We explored the core matrisome (ECM proteome) of human fetal nucleus pulposus (NP) for proteins of regenerative potential and found a great number of such proteins to be upregulated or Scientific Reports | (2021) 11:19013

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