DIPPER, a Spatiotemporal Proteomics Atlas of Human Intervertebral Discs for Exploring Ageing and Degeneration Dynamics

Overview

Journal Elife

Specialty Biology

Date 2020 Dec 31

PMID 33382035

Citations 30

Authors

Vivian Tam

Peikai Chen

Anita Yee

Nestor Solis

Theo Klein

Mateusz Kudelko

Rakesh Sharma

Wilson Cw Chan

Christopher M Overall

Lisbet Haglund

Pak C Sham

Kathryn Song Eng Cheah

Danny Chan

Affiliations

Soon will be listed here.

Abstract

The spatiotemporal proteome of the intervertebral disc (IVD) underpins its integrity and function. We present DIPPER, a deep and comprehensive IVD proteomic resource comprising 94 genome-wide profiles from 17 individuals. To begin with, protein modules defining key directional trends spanning the lateral and anteroposterior axes were derived from high-resolution spatial proteomes of intact young cadaveric lumbar IVDs. They revealed novel region-specific profiles of regulatory activities and displayed potential paths of deconstruction in the level- and location-matched aged cadaveric discs. Machine learning methods predicted a 'hydration matrisome' that connects extracellular matrix with MRI intensity. Importantly, the static proteome used as point-references can be integrated with dynamic proteome (SILAC/degradome) and transcriptome data from multiple clinical samples, enhancing robustness and clinical relevance. The data, findings, and methodology, available on a web interface (http://www.sbms.hku.hk/dclab/DIPPER/), will be valuable references in the field of IVD biology and proteomic analytics.

Citing Articles

Biglycan fragment modulates TGF-β activity in intervertebral disc via an eIF6-coupled intracellular path.

Zhu M, Wu S, Tam W, Wong C, Liao P, Cheah K Sci Adv. 2025; 11(7):eadq8545.

PMID: 39951526 PMC: 11827866. DOI: 10.1126/sciadv.adq8545.

Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration.

Dube C, Gilbert H, Rabbitte N, Baird P, Patel S, Herrera J Arthritis Res Ther. 2025; 27(1):28.

PMID: 39930483 PMC: 11809052. DOI: 10.1186/s13075-025-03489-9.

Effects of GDF6 on active protein synthesis by cells of degenerated intervertebral disc.

Tam V, Chopra N, Sima S, Chen P, Sharma R, Chan D Eur Spine J. 2025; .

PMID: 39920317 DOI: 10.1007/s00586-025-08715-1.

Integrating bioinformatics and experimental validation to Investigate IRF1 as a novel biomarker for nucleus pulposus cells necroptosis in intervertebral disc degeneration.

Zhou K, Wu S, Wu Z, Ran R, Song W, Dong H Sci Rep. 2024; 14(1):30138.

PMID: 39627301 PMC: 11615235. DOI: 10.1038/s41598-024-81681-8.

Senescence in Intervertebral Disc Degeneration: A Comprehensive Analysis Based on Bioinformatic Strategies.

Zhao Z, Wang Y, Wang Z, Zhang F, Ding Z, Fan T Immun Inflamm Dis. 2024; 12(11):e70072.

PMID: 39555740 PMC: 11571097. DOI: 10.1002/iid3.70072.

References

Zhu M, Tang D, Wu Q, Hao S, Chen M, Xie C . Activation of beta-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult beta-catenin conditional activation mice. J Bone Miner Res. 2008; 24(1):12-21. PMC: 2640321. DOI: 10.1359/jbmr.080901. View

Scott J, Gabrielides C, Davidson R, Swingler T, Clark I, Wallis G . Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease. Ann Rheum Dis. 2010; 69(8):1502-10. PMC: 3789136. DOI: 10.1136/ard.2009.119966. View

Kleifeld O, Doucet A, Auf dem Keller U, Prudova A, Schilling O, Kainthan R . Isotopic labeling of terminal amines in complex samples identifies protein N-termini and protease cleavage products. Nat Biotechnol. 2010; 28(3):281-8. DOI: 10.1038/nbt.1611. View

Minogue B, Richardson S, Zeef L, Freemont A, Hoyland J . Characterization of the human nucleus pulposus cell phenotype and evaluation of novel marker gene expression to define adult stem cell differentiation. Arthritis Rheum. 2010; 62(12):3695-705. DOI: 10.1002/art.27710. View

Grimsrud C, Romano P, DSouza M, Puzas J, Schwarz E, Reynolds P . BMP signaling stimulates chondrocyte maturation and the expression of Indian hedgehog. J Orthop Res. 2001; 19(1):18-25. DOI: 10.1016/S0736-0266(00)00017-6. View

McCann M, Patel P, Frimpong A, Xiao Y, Siqueira W, Seguin C . Proteomic signature of the murine intervertebral disc. PLoS One. 2015; 10(2):e0117807. PMC: 4331544. DOI: 10.1371/journal.pone.0117807. View

Saleem S, Aslam H, Khan Rehmani M, Raees A, Alvi A, Ashraf J . Lumbar disc degenerative disease: disc degeneration symptoms and magnetic resonance image findings. Asian Spine J. 2013; 7(4):322-34. PMC: 3863659. DOI: 10.4184/asj.2013.7.4.322. View

Teraguchi M, Yoshimura N, Hashizume H, Muraki S, Yamada H, Minamide A . Prevalence and distribution of intervertebral disc degeneration over the entire spine in a population-based cohort: the Wakayama Spine Study. Osteoarthritis Cartilage. 2013; 22(1):104-10. DOI: 10.1016/j.joca.2013.10.019. View

Wyatt A, Yerbury J, Wilson M . Structural characterization of clusterin-chaperone client protein complexes. J Biol Chem. 2009; 284(33):21920-21927. PMC: 2755916. DOI: 10.1074/jbc.M109.033688. View

10.

Naba A, Clauser K, Hoersch S, Liu H, Carr S, Hynes R . The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. Mol Cell Proteomics. 2011; 11(4):M111.014647. PMC: 3322572. DOI: 10.1074/mcp.M111.014647. View

11.

Barber R, Harmer D, Coleman R, Clark B . GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues. Physiol Genomics. 2005; 21(3):389-95. DOI: 10.1152/physiolgenomics.00025.2005. View

12.

Molinos M, Almeida C, Caldeira J, Cunha C, Goncalves R, Barbosa M . Inflammation in intervertebral disc degeneration and regeneration. J R Soc Interface. 2015; 12(108):20150429. PMC: 4528607. DOI: 10.1098/rsif.2015.0429. View

13.

Schneiderman G, Flannigan B, Kingston S, Thomas J, Dillin W, WATKINS R . Magnetic resonance imaging in the diagnosis of disc degeneration: correlation with discography. Spine (Phila Pa 1976). 1987; 12(3):276-81. DOI: 10.1097/00007632-198704000-00016. View

14.

Yee A, Lam M, Tam V, Chan W, Chu I, Cheah K . Fibrotic-like changes in degenerate human intervertebral discs revealed by quantitative proteomic analysis. Osteoarthritis Cartilage. 2015; 24(3):503-13. DOI: 10.1016/j.joca.2015.09.020. View

15.

Robinson K, Sun M, Barnum C, Weiss S, Huegel J, Shetye S . Decorin and biglycan are necessary for maintaining collagen fibril structure, fiber realignment, and mechanical properties of mature tendons. Matrix Biol. 2017; 64:81-93. PMC: 5705405. DOI: 10.1016/j.matbio.2017.08.004. View

16.

Silagi E, Shapiro I, Risbud M . Glycosaminoglycan synthesis in the nucleus pulposus: Dysregulation and the pathogenesis of disc degeneration. Matrix Biol. 2018; 71-72:368-379. PMC: 6119535. DOI: 10.1016/j.matbio.2018.02.025. View

17.

Chen J, Yan W, Setton L . Molecular phenotypes of notochordal cells purified from immature nucleus pulposus. Eur Spine J. 2006; 15 Suppl 3:S303-11. PMC: 2335373. DOI: 10.1007/s00586-006-0088-x. View

18.

Taye N, Karoulias S, Hubmacher D . The "other" 15-40%: The Role of Non-Collagenous Extracellular Matrix Proteins and Minor Collagens in Tendon. J Orthop Res. 2019; 38(1):23-35. PMC: 6917864. DOI: 10.1002/jor.24440. View

19.

Hiyama A, Sakai D, Risbud M, Tanaka M, Arai F, Abe K . Enhancement of intervertebral disc cell senescence by WNT/β-catenin signaling-induced matrix metalloproteinase expression. Arthritis Rheum. 2010; 62(10):3036-47. PMC: 3622204. DOI: 10.1002/art.27599. View

20.

Kanehisa M, Sato Y, Furumichi M, Morishima K, Tanabe M . New approach for understanding genome variations in KEGG. Nucleic Acids Res. 2018; 47(D1):D590-D595. PMC: 6324070. DOI: 10.1093/nar/gky962. View